Open Access

Epidemiology and genetic diversity of bovine leukemia virus

Virology Journal201714:209

https://doi.org/10.1186/s12985-017-0876-4

Received: 31 July 2017

Accepted: 24 October 2017

Published: 2 November 2017

Abstract

Bovine leukemia virus (BLV), an oncogenic member of the Deltaretrovirus genus, is closely related to human T-cell leukemia virus (HTLV-I and II). BLV infects cattle worldwide and causes important economic losses. In this review, we provide a summary of available information about commonly used diagnostic approaches for the detection of BLV infection, including both serological and viral genome-based methods. We also outline genotyping methods used for the phylogenetic analysis of BLV, including PCR restriction length polymorphism and modern DNA sequencing-based methods. In addition, detailed epidemiological information on the prevalence of BLV in cattle worldwide is presented. Finally, we summarize the various BLV genotypes identified by the phylogenetic analyses of the whole genome and env gp51 sequences of BLV strains in different countries and discuss the distribution of BLV genotypes worldwide.

Keywords

Bovine leukemia virus (BLV)BLV diagnostic approchesBLV genotyping methodsBLV epidemiology

Background

Bovine leukemia virus (BLV) is a retrovirus, an oncogenic member of the Deltaretrovirus genus, and the causative agent of enzootic bovine leukosis (EBL) [1, 2]. The Deltaretrovirus genus also includes human T-cell lymphotropic virus types I and II (HTLV-I and -II) and simian T-cell lymphotropic virus (STLV) [3, 4]. EBL is a contagious lymphoproliferative disease of cattle, characterized by B-cell lymphosarcoma, which occurs throughout the world [2, 5]. Although BLV can infect various immune cell populations, including CD5+ IgM+ and CD5 IgM+ B-cells; CD2+, CD3+, CD4+, CD8+, and γ/δ T-cells; monocytes; and granulocytes in peripheral blood and lymphoid tissues of cattle [611], BLV-induced tumors usually arise from the CD5+ IgM+ B-cell subpopulation [12].

BLV infection can result in a variety of clinical outcomes [2]. The majority of BLV-infected cattle are asymptomatic carriers of the virus, neither showing any clinical signs nor any changes in lymphocyte count; however, a recent study showed that although lymphocyte counts were not elevated in BLV-infected but clinically normal cattle, CD5+ IgM+ B-cells were increased [11], and there is substantial evidence suggesting that BLV-infected but clinically normal cattle may exhibit a degree of immunological dysregulation leading to economic losses for various reasons including reduced milk production [13], a high incidence of infectious disease [14], and reproductive inefficiency [15]. Approximately one-third of infected cattle develop a benign form of non-malignant proliferation of untransformed B-lymphocytes, termed persistent lymphocytosis (PL). PL is typically characterized by a permanent and stable increase in the number of CD5+ IgM+ B-cells circulating in the peripheral blood. Less than 5% of infected cattle develop malignant B-cell lymphoma originating from mono- or oligo-clonal accumulation of CD5+ IgM+ B-cells after a relatively long period of latency. This malignant form of B-cell lymphoma is predominantly detected in cattle over 4–5 years old [16]. Such malignancies induce disruption of the spleen and remarkable enlargement of the lymph nodes, which can be visible under the skin. BLV-induced neoplastic cells can penetrate into the abomasums, right auricle of the heart, intestine, kidney, lung, liver, and uterus. The clinical signs of BLV-induced tumors are varied and primarily involve digestive disturbance, weight loss, weakness, reduced milk production, loss of appetite, and enlarged lymph nodes [17].

BLV genome structure

The BLV genome consists of 8714 nucleotides (nt) [18] including essential structural protein and enzyme coding genes and a pX region, flanked by two identical long terminal repeats (LTRs) (Fig. 1a). The structural protein and enzyme coding genes, namely, gag, pro, pol, and env, have essential and indispensable roles in the viral lifecycle, viral infectivity, and the production of infectious virions [1924]. The gag gene of BLV is translated as the precursor, Pr45 Gag, and processed to generate three mature proteins [19, 23]: the matrix protein, p15, which binds viral genomic RNA and interacts with the lipid bilayer of the viral membrane [25]; the capsid protein, p24, which is the major target of the host immune response, with high antibody titers against this molecule found in the serum of infected animals [26, 27]; and the nucleocapsid protein, p12, which binds to packaged genomic RNA [28] (Fig. 1b). The env gene encodes the mature extracellular protein, gp51, and a transmembrane protein, gp30 [19]. The pX region, which is located between env and the 3′ LTR [2], encodes the regulatory proteins Tax and Rex, and the accessory proteins R3 and G4 (Fig. 1a). The regulatory proteins are important for regulation of viral transcription, transformation of BLV-induced leukemogenesis, and nuclear export of viral RNA into the cytoplasm [2936]. The R3 and G4 accessory proteins contribute to the maintenance of high viral loads [37, 38]. In addition to the genes described above, the BLV genome also contains RNA polymerase-III-encoded viral microRNAs (miRNAs) between the env and pX regions. Viral miRNAs are strongly expressed in preleukemic and malignant cells, and may have roles in tumor onset and progression [39, 40] through their effects on proviral load and consequently viral replication in the natural host [41]. Besides, Van Driessche et al. revealed the recruitment of positive epigenetic marks on BLV miRNA cluster, inducing strong antisense promoter activity [42]. They also identified cis-acting elements of an RNAPII-dependent promoter [42].
Fig. 1

Schematic representations of the BLV genome structure (a) and viral particle (b). The structural and enzymatic genes, gag, pro, pol, and env; regulatory genes, tax and rex; accessory genes R3 and G4; and microRNA (miRNA) are indicated in (a). Proteins encoded by structural and enzymatic genes, including the Env glycoproteins (gp51 and gp30) encoded by the env gene, the Gag proteins (p12, p24, and p15) encoded by the gag gene, reverse transcriptase and integrase (RT-IN) encoded by the pol gene, and protease (Pro) encoded by the pro gene are indicated in (b)

BLV diagnosis

A variety of techniques have been developed for diagnosis of BLV and implemented worldwide. These diagnostic methods can be assigned into two main groups, consisting of antibody-based serological tests and detection of the proviral genome by nucleic acid-based polymerase chain reaction (PCR) assays (summarized in Table 1).
Table 1

Summary of common techniques used for diagnosis of BLV prevalence

Diagnostic assay

Sample

Target

Advantages

Disadvantages

References

Type

Assay

Serological test

AGID

Serum

Antibodies (p24, gp51)

Specific, simple, and easy to perform Large scale screening Less expensive

Rapid

Less sensitive and inconclusive Cannot evaluate disease states of infected cattle

Aida et al., 1989 [47]

Wang et al., 1991 [48]

Monti et al., 2005 [49]

Kurdi et al., 1999 [50]

Jimba et al., 2012 [43]

Naif et al., 1990 [55]

ELISA

Serum Milk Bulk milk

Antibodies (p24, gp51)

Specific and sensitive Large scale screening Time saving

False negatives (cattle in early infection phase) False positive (maternally derived antibodies) Cannot evaluate disease states of infected cattle A number of controls and a plate reader required Results require interpretation

Naif et al., 1990 [55]

Burridge et al., 1982 [56]

Schoepf et al., 1997 [53]

Kurdi et al., 1999 [50]

Monti et al., 2005 [49]

Jimba et al., 2012 [43]

Zaghawa et al., 2002 [52]

PHA

Virus particle

BLV glycoprotein

Sensitive Specific detection of BLV Large scale titration Less expensive

Rapid

Affected by pH and temperature Hemagglutination activity reduced by trypsin, potassium periodate, and neuraminidase

Fukai et al., 1999 [51]

RIA

Serum

Antibodies (p24)

Sensitive Able to detect BLV during the early period of infection

Cannot be used for mass screening

Levy et al., 1977 [54]

Nguyen et al., 1993 [57]

Proviral DNA detection

Single PCR; Semi-nested PCR; Nested PCR

Blood PBMC Tumor sample Buffy coat Milk somatic cells

Semen Saliva Nasal secretions

Provirus

Direct, fast, sensitive A variety of samples can be used BLV detection during the early phase of infection or in the presence of colostrum antibodies

Can detect new infections, before the development of antibodies to BLV

Unable to detect BLV when the proviral load is too low

Cross contamination occurs easily Requires specific primers Requires equipment (PCR machine) False negatives in the presence of PCR inhibitory substances in samples Requires internal control Needs confirmatory testing, such as sequencing

Monti et al., 2005 [49]

Kurdi et al., 1999 [50]

Zaghawa et al., 2002 [52]

Tajima et al., 1998 [64]

Tajima et al., 2003 [61]

Real-time PCR

Blood PBMC Tumor sample Buffy coat Milk

Somatic cells Semen Saliva Nasal secretions

Provirus

Direct, fast, sensitive Low risk of contamination A variety of samples can be used Distinguishes EBL from SBL BLV can be detected during the early phase of infection or in the presence of colostrum antibodies Quantitative measurement of proviral load

Requires internal control Requires positive controls of different concentrations Requires specific primers and probes Require equipment (real-time PCR machine) Expensive

Complicated sample preparation procedure

Somura et al., 2014 [68]

Lew et al., 2004 [69]

Jimba et al., 2010 [70]

Jimba et al., 2012 [43]

Tawfeeq et al., 2013 [67]

Brym et al., 2013 [66]

Takeshima et al., 2015 [71]

Direct blood-based PCR

Blood

Provirus

Cost-effective No need for DNA purification Low risk of contamination

Unable to detect BLV when the proviral load is too low

Results in failure if there are mismatches between the PCR primers and BLV sequences Relatively low sensitivity

Nishimori et al., 2016 [72]

Takeshima et al., 2016 [73]

AGID agar gel immunodiffusion, BLV bovine leukemia virus, EBL enzootic bovine leukosis, ELISA enzyme-linked immunosorbent assay, PHA passive hemagglutination assay, RIA radio immunoassay

Serological tests

For indirect BLV diagnostic methods, particularly antibody-based tests, antibodies recognizing the p24 capsid protein encoded by the gag gene and the extracellular gp51 protein encoded by env-gp51 are targeted. This is because antibodies against these proteins are produced shortly after BLV infection, can be detected 2–3 weeks post-infection, and remain detectable for the life of the host animal [43]. In addition, the p24 capsid protein is a major target for host immune responses, inducing high antibody titers [44], and gp51 invokes the expression of massive amounts of specific antibodies in infected animals [24, 45, 46]. Therefore, antibodies against these proteins are targeted for BLV diagnostics using conventional serological techniques such as agar gel immunodiffusion (AGID) [43, 4750], passive hemagglutination assay (PHA) [43, 51], enzyme-linked immunosorbent assay (ELISA) [43, 49, 50, 52, 53], and radio immunoassay (RIA) [54]. Most of these serological methods aim to detect antibodies in bovine serum and milk, and the supernatants of BLV-infected cell cultures. AGID is relatively inexpensive and can be used to screen many serum samples simultaneously; however, it is not sufficiently sensitive [55] and it is not suitable for analysis of milk samples. ELISA is a highly sensitive and easily implemented procedure, and can be used to analyze both serum and milk samples; however, it requires a number of controls and produces both false-negative result in serum samples from cattle in the early phase of infection [55] and false-positive results in calves that contain maternally-derived antibodies [56]. PHA aims to detect BLV glycoproteins, but, PHA test efficiency is sensitive to pH, temperature, and trypsin. RIA is suitable for diagnosing BLV soon after animals are exposed, but not suitable for the purpose of mass screening [57]. Overall, these antibody-based detection methods cannot be used to test calves less than 6 months old, due to the presence of maternal antibodies, which may trigger false-positive results [58].

Proviral DNA detection

BLV can integrate into dispersed sites within the host genome [59] and appears to be transcriptionally silent in vivo [6062] and remain in cellular genomes, even in the absence of detectable BLV antibodies. Indeed, transcription of the BLV genome in fresh tumor or peripheral blood mononuclear cell samples from infected individuals is almost undetectable by conventional techniques [60, 63]. Interestingly, one copy of the full-length proviral genome can be detected in BLV-infected cattle throughout the course of the disease [64]. Another study also demonstrated that BLV-induced tumors and BLV-infected cells contain provirus, with approximately four copies of proviral DNA in each tumor [65]. Hence, in addition to the routine diagnosis of BLV infection using the conventional serological techniques described above, nucleic acid-based PCR methods can greatly accelerate the detection of BLV prevalence.

A variety of PCR methods, including standard PCR [49, 50], nested PCR [33, 52, 64], real-time quantitative PCR (qPCR) [43, 6671], and direct blood-based PCR [72, 73], have been extensively applied worldwide for BLV detection (Table 1). A variety of genes in the BLV genome are targeted for detection of BLV infection prevalence by direct diagnostic PCR methods, including the LTR region [43, 70, 71, 7377], and the gag [78], pol [69, 79, 80], env [55, 79], and tax [68, 79] genes.

Importantly, the BLV provirus copy number is generally very low compared with that of host genes therefore, the majority of PCR systems designed to detect BLV used a nested design [64, 74, 76]. These nested assays are extremely sensitive, but also obtain false-positive results due to DNA contamination. However, the method requires expensive real-time PCR machines and reagents and involves difficult sample preparation protocols. Recently, a novel blood-based PCR system that amplifies target DNA regions without a requirement for DNA isolation and purification was developed [72, 73]. The assay can detect BLV provirus with high specificity and at low cost, facilitating timely identification of BLV-infected cattle.

As discussed above, PCR-based genome screening methods for diagnosis of BLV broaden the range of samples that can be used, increase testing sensitivity, specificity, and efficiency, and are less time consuming. PCR also allows the detection of BLV infection in cattle several weeks before it is possible to detect antibodies [81]; however, PCR-based provirus screening involves complicated sample preparation processes, which can lead to false-positive results if cross contamination occurs. In addition, PCR-based BLV detection methods require specific laboratory facilities, including PCR machines, and the design of specific primers and probes is also necessary. The CoCoMo algorithm, is a method used to design degenerate primer sets that amplify all available sequences within a target region. Recently, the BLV-CoCoMo-qPCR assay was developed to measure the BLV proviral load with extremely high sensitivity and to amplify both known and novel BLV variants [43, 70, 71]. This assay enabled us to demonstrate that the proviral load correlates not only with BLV infection capacity but also with BLV disease progression [43, 82], and identification of risk factor associated with increased BLV proviral load in infected cattle [82, 83] and detection of BLV provirus in nasal secretion and saliva samples [84].

Other methods

In addition to the techniques described above, other BLV diagnostic approaches, including detection of viral proteins by western blotting [21, 31, 33, 85], a syncytium formation assay [85], and detection of BLV antigens by indirect immunofluorescent assay [47], have also been described.

BLV genotyping and identification of ten distinct genotypes

Studies of BLV genotypes for phylogenetic and epidemiological analyses have primarily focused on the env gene, the env gp51 gene in particular, because of its biological functions. The extracellular gp51 protein has key roles in the viral lifecycle and is indispensable for viral entry into host cells [20, 86]. In addition, because of the surface localization of the gp51 glycoprotein, it is also the target of neutralizing antibodies [87]. The conformational epitopes, F, G, and H, located in the N-terminal half of gp51, are important in syncytium formation and viral infectivity [87, 88]. Therefore, the env gp51 sequence region is frequently used for BLV phylogenetic analysis.

Over the years, a number of methods have been applied for BLV genotyping, as summarized in Table 2. In the early days of BLV genotyping, researchers clustered or genotyped BLV strains from different geographical regions based on restriction fragment length polymorphisms (RFLP) of PCR-products, generated using various restriction enzymes [86, 8996]. BLV clusters and genotypes were named after the geographical region of sample isolation, such as “Argentine type” or “Australian type”, or with reference to phylogenetic clustering (e.g., “cluster one”). A total of seven BLV clusters/genotypes were determined by PCR-RFLP [91]; however, PCR-RFLP genotyping studies were not consistent or comprehensive.
Table 2

Summary of BLV genotyping methods

Genotyping method

Amplified BLV region

Amplicon size (bp)

Enzymes

Phylogenetic approaches

Classification result

Reference

PCR-RFLP

Partial env-gp51 region

444

BamHI, BglI, HaeIII, BclI, PvuII, DraI, HindIII, HpaII, StuI, TaqI

 

7 groups: A, B, C, D, E, F, G

Fechner et al., 1997 [90]

Licursi et al., 2002 [91]

Asfaw et al., 2005 [95]

RFLP + sequencing

Partial gp51 sequencing

400–444

BamHI, BclI, PvuII, GmbH

NJ; MP; ML

RFLP-based type: Australian type, Argentine type, Belgium type, Japanese type; Sequence-based type: Argentine cluster, European cluster, Japan and German isolate cluster; groups I–IV; or genotypes 1–8

Monti et al., 2005 [49]

Felmer et al., 2005 [93]

Camargos et al., 2007 [122]

PCR-sequencing

Partial gp51 sequencing

346–444

 

NJ; ML; BI

Japanese group, Argentine group, European group; or genotypes 1–8

Camargos et al., 2002 [121]

Licursi et al., 2003 [92]

Matsumura et al., 2011 [98]

Rola-Luszczak et al., 2013 [99]

Polat et al., 2015 [74]

Ochirkhuu et al., 2016 [77]

Polat et al., 2016 [75, 76]

 

Sequencing of partial or full gp51 gene sequences

444–903

 

NJ; ML; BI

Up to 10 BLV genotypes

Moratorio et al., 2010 [126]

Balic et al., 2012 [97]

Lee et al., 2015 [100]

Lee et al., 2016 [101]

 

Sequencing of env (full gp51 and/or gp30 genes)

up to 1548

 

NJ; ML; BI

Consensus cluster, US Californian cluster, European cluster, Costa Rican cluster; or genotypes 1–10

Zhao et al., 2007 [109]

Rodriguez et al., 2009 [96]

Yang et al., 2016 [131]

Full BLV genome sequencing

BLV complete genome

8714

 

ML

genotypes −1, −2, −4, −6, −9, and −10

Polat et al., 2016 [75, 76]

BI Bayesian inference, BLV bovine leukemia virus, NJ neighbor-joining, ML maximum-likelihood, MP maximum-parsimony, RFLP restriction fragment length polymorphism

In 2007, Rodriguez et al. reported sequencing of the env gene (all of gp51 and part of gp30) of 28 BLV field strains, performed phylogenetic analysis of these sequences in comparison with published sequence data representative of established genetic groups by neighbor-joining, maximum likelihood, and Bayesian inference methods, and assigned BLV sequences into seven genotypes [97]. Subsequently, a new genotype, genotype-8, was identified in BLV samples from Croatia by Balic et al. [98], who concluded that BLV may be more divergent than previously thought, speculating that additional genotypes might be discovered in the future. Indeed, the presence of eight BLV genotypes was later confirmed in different geographical locations [74, 77, 99101]. Finally, in 2016, the novel BLV genotypes, genotype-9 and -10, were discovered in Bolivia [75], Thailand [102], and Myanmar [76], a totaling ten BLV genotype clusters (Fig. 2). Previously, almost all phylogenetic studies of BLV genotypes focused on the partial or entire env gene. However, for the first time in their study [75, 76], Polat et al. successfully concluded the existence of genotypes-1, −2, −4, −6, −9 and −10 among ten BLV genotypes (Fig. 3) by phylogenetic analysis using complete sequences of BLV strains newly determined by next generation sequencing and sequencing cloned, overlapping PCR products in their studies, and using complete BLV genome sequences available in the database (NCBI & DDBJ). These phylogenetic analysis of complete BLV genomes demonstrated that each BLV genotype encodes specific amino acid substitutions in both structural and non-structural gene regions.
Fig. 2

Maximum likelihood phylogenetic tree constructed based on partial BLV env sequences identified in geographical locations around the world. A maximum likelihood (ML) phylogenetic tree was constructed based on sequences from known BLV strains, representing ten different BLV genotypes derived from viruses isolated worldwide. Nucleotide sequences were obtained from the GenBank nucleotide sequence database. Sequences are labeled with their accession numbers and countries of origin. Genotypes are indicated by numbers to the right of the figure. One thousand replications were performed to calculate bootstrap values (indicated on the tree). The bar at the bottom of the figure indicates evolutionary distance

Fig. 3

Maximum likelihood (ML) phylogenetic tree constructed from complete BLV genomic sequences. The ML phylogenetic tree was constructed using complete BLV genomic sequences from the GenBank nucleotide sequence database. One thousand replications were performed to calculate bootstrap values (indicated on the tree). The strains identified in this study are indicated by the sample identification number and country name. Genotypes are indicated by numbers to the right of the figure. The bar at the bottom of the figure indicates evolutionary distance

BLV prevalence

BLV has spread to all continents via the trade in breeding animals, and is prevalent in cattle worldwide. BLV infection levels vary between and within countries, as shown in Table 3 (data obtained on March 17th, 2017; updated and detailed information is available at http://www.oie.int/wahis_2/public/wahid.php/Diseaseinformation/statuslist) [17, 103]. BLV eradication programs and control measures have been established in European Community member countries since the second half of the twentieth century, and eradication programs have been very successful in the majority of western Europe [104107]; indeed, some countries, including Denmark, Finland, Switzerland, Estonia, The Netherlands and Poland, are completely free of BLV [104, 108110]. Despite the majority of countries in Western Europe being free from disease, EBL still exists in eastern European nations, including Poland, Ukraine, and Croatia [98, 100, 111113]. In addition, in Italy, Portugal, Belarus, Latvia, Greece, Romania, and Bulgaria, BLV is present, although disease is either absent or limited to specific areas [103].
Table 3

Detailed information on BLV infection levels worldwide

Geographical division

Country

Within country

BLV prevalencea

References

Europe

Andorra

Nationwide

BLV-free, 1994

OIE, 2009 [103]

Cyprus

Nationwide

BLV-free, 1995

OIE, 2009 [103]

Czech Republic

Nationwide

BLV-free, 2010

OIE, 2009 [103]

Denmark

Nationwide

BLV-free, 1990

OIE, 2009 [103]

Estonia

Nationwide

BLV-free, 2013

OIE, 2009 [103]

Finland

Nationwide

BLV-free, 2008

OIE, 2009 [103]

Ireland

Nationwide

BLV-free, 1999

OIE, 2009 [103]

Norway

Nationwide

BLV-free, 2002

OIE, 2009 [103]

Spain

Nationwide

BLV-free, 1994

OIE, 2009 [103]

Switzerland

Nationwide

BLV-free, 2005

OIE, 2009 [103]

Sweden

Nationwide

BLV-free, 2007

OIE, 2009 [103]

Slovenia

Nationwide

BLV-free, 2006

OIE, 2009 [103]

UK

Nationwide

BLV-free, 1996

OIE, 2009 [103]

The Netherlands

Nationwide

BLV-free, 2009

OIE, 2012 [17]

Poland

 

BLV-free, 2017

EFSA Panel on Animal Health and Welfare, 2017 [110]

Ukraine

 

Present

OIE, 2012 [17]; Rola-Luszczak et al., 2013 [100]

Croatia

 

Present

OIE, 2012 [17]; Balik et al., 2012

Italy

 

Present

OIE, 2009 [103]; Molteni et al., 1996 [144]

Portugal

 

Present

OIE, 2009 [103]

Belarus

 

Present

OIE, 2012 [17]; Rola-Luszczak et al., 2013 [100]

Latvia

 

Present

OIE, 2009 [103]

Romania

 

Restricted to certain area

OIE, 2009 [103]

Bulgaria

 

Present

OIE, 2009 [103]

Greece

 

Present

OIE, 2009 [103]

Oceania

Australia

 

BLV-free in dairy cattle, 2013

EPAHW, 2015 [113]

New Zealand

 

BLV-free, 2008

Chethanond, 1999 [114]

North America

USA

 

83.9% dairy cattle; 39% beef cattle, 2007

APHIS, 2008 [115]

Canada

Nationwide

89% at herd level

APHIS, 2008 [115]

 

Nationwide

78% at herd level, 1998–2003

Nekouei, 2015 [13]

 

Saskatchewan

37.2% at individual level, 2001

VanLeeuwen et al., 2001 [116]

 

Maritime

20.8% at individual and 70.0% at herd level, 1998–1999

VanLeeuwen et al., 2005 [117]

 

Maritime

30.4% at individual and 90.8% at herd level, 2013

Nekouei, 2015 [118]

Mexico

Nationwide

36.1% of dairy and 4.0% of beef cattle, 1983

Suzan et al., 1983 [119]

South America

Brazil

 

17.1% to 60.8%, 1980–1989 and 1992–1995

Sammara et al., 1997 [120] ; D’Angelino et al., 1998 [121]

Argentina

Buenos Aires

77.4% at individual and 90.9% at herd level, 2007

Polat et al., 2016 [75]

 

Multiple regions

32.85% at individual and 84% at herd level, 1998–1999

Trono et al., 2001 [124]

Chile

Southern region

27.9% at individual level, 2009

Polat et al., 2016 [75]

Bolivia

Multiple regions

30.7% at individual level, 2008

Polat et al., 2016 [75]

Peru

Multiple regions

42.3% at individual level, 2008

Polat et al., 2016 [75]

 

Multiple regions

31.0% at individual level, 1983

Ch, 1983 [125]

Venezuela

Nationwide

33.3% at individual level, 1978

Marin et al., 1978 [126]

Uruguay

 

Present

Moratorio et al., 2010 [127]

Paraguay

Asuncion

54.7% at individual level, 2008

Polat et al., 2016 [75]

Colombia

Narino

19.8% at individual level, 2013

Benavides et al., 2013 [131]

Africa

South Africa

 

BLV-free, 2012

OIE, 2012 [17]

Tunisia

 

BLV-free, 2005

OIE, 2009 [103]

Egypt

 

BLV-free, 1997

OIE, 2009 [103]

Asia

Kazakhstan

 

BLV-free, 2007

OIE, 2009 [103]

Kyrgyzstan

 

BLV-free, 2008

OIE, 2009 [103]

China

 

49.1% of dairy and 1.6% of beef cattle, 2013–2014

Yang et al., 2016 [132]

Japan

Nationwide

40.9% of dairy and 28.7% of beef cattle, 2009–2011

Murakami et al., 2013 [136]

 

Nationwide

79.1% of dairy herd, 2007

Kobayashi et al., 2010 [134]

 

Nationwide

28.6% overall; 34.7% of dairy, 16.3% of beef, and 7.9% of fattening beef cattle, 2007

Murakami et al., 2011 [135]

 

Nationwide

73.3% at individual cattle, 2012–2014

Ohno et al., 2015 [83]

Mongolia

 

3.9% of dairy cattle, 2014

Ochirkhuu et al., 2016 [77]

Cambodia

 

5.3% of draught cattle, 2000

Meas et al., 2000 [137]

Taiwan

 

5.8% of dairy cattle, 1986

Wang et al., 1991 [48]

Iran

Nationwide

Between 22.1% to 25.4%, 2012–2014

Nekoei et al., 2015 [138]; Mousavi et al., 2014 [139].

 

Khorasan Razavi

29.8% of dairy cattle, 2009

Mousavi et al., 2014 [139].

 

Khorasan Shomali

1.5% of dairy cattle, 2009

Mousavi et al., 2014 [139].

Thailand

 

58.7% of cattle, 2013–2014

Lee et al., 2016 [102]

Philippines

 

4.8% to 9.7% of cattle, 2010–2012

Polat et al., 2015 [74]

Myanmar

 

9.1% at individual level 2016

Polat et al., 2016 [76]

Korea

 

54.2% of dairy cattle and 86.8% of dairy herds; 0.14% of beef cattle, 2014

Lee et al., 2015 [101]

Middle East

Israeli

 

5% at individual level

Trainin & Brenner, 2005 [140]

Saudi Arabia

 

20.2% of dairy cattle, 1990

Hafez et al., 1990 [141]

Turkey

 

48.3% of dairy herd

Burgu et al., 2005 [142]

BLV prevalence in this table shows BLV infection in certain specific period. Therefore, there might be a change in BLV prevalence in different times

APHIS Animal and Plant Health Inspection Service, BLV bovine leukemia virus, EFSA European Food Safety Authority, EPAHW European Panal on Animal Health and Welfare, OIE The World Organisation for Animal Health

Note: aBLV prevalence in each sample collection year; however, no information about sample collection year was provided in some cases

Nationwide BLV eradication and control programs were introduced in Australia and New Zealand in 1983 and 1996, respectively, and 99.7% of Australian dairy herds were declared free from EBL in December 2013, while those in New Zealand have been free from BLV-induced EBL since 2008 [113, 114].

In North America, an epidemiological study of BLV prevalence in US dairy cattle conducted by the Department of Agriculture’s National Animal Health Monitoring System demonstrated that 83.9% of dairy cattle were BLV-positive at herd level and 39% of beef herds had at least one BLV-infected animal [115]. In Canada, studies of BLV prevalence revealed that up to 37.2% of cows and 89% of herds were BLV-positive [116118]. BLV is also present in both beef and dairy cattle in Mexico [119]; however, disease is either absent or limited to specific areas [17] (accessed on 22 Dec 2016).

In South America, relatively high levels of BLV prevalence have been observed, and BLV-induced leukosis is present in the majority of countries. In Brazil, BLV prevalence varies among states, with infection rates ranging from 17.1% to 60.8% [120123]. Individual and herd level BLV prevalence in Argentina are as high as 77.4% and 90.9%, respectively [75, 95, 124]. Moreover, individual infection rates between 19.8% and 54.7% have been reported in Chile, Bolivia, Peru, Venezuela, Uruguay, Paraguay, and Columbia [75, 94, 125131].

BLV infection is widespread in Chinese dairy farms. Infection rates are up to 49.1% among individual dairy cattle, while 1.6% of beef cattle are BLV-positive [132]. Moreover, serological tests revealed that 20.1% of yaks in China were BLV-positive [133]. Epidemiological studies in Japan revealed varying levels of BLV prevalence throughout the country, based on different detection methods [83, 134136], and BLV infection rates of 40.9% of dairy and 28.7% of beef cattle, with infection rates in animals over 2-years-old reaching 78% in dairy herds and 69% in beef cattle herds [136]. Less than 6% of cattle were infected with BLV in Mongolia (3.9%) [77], Cambodia (5.3%) [137], and Taiwan (5.8%) [48], while a serological survey in Iran revealed that the prevalence of BLV was between 22.1% and 25.4% in that country [138, 139]. Lee et al. [102] demonstrated an average prevalence of BLV of 58.7% in Thailand, reaching maxima of 87.8% and 100% of cattle when assayed using PCR and ELISA, respectively. In Korea, 54.2% of dairy cattle and 86.8% of dairy herds were BLV-positive, whereas only 0.14% of beef cattle were infected with BLV [101]. BLV infection levels in The Philippines ranged from 4.8% to 9.7% [74] while it was 9.1% in Myanmar [76]. BLV infections in Middle Eastern countries are relatively low. The prevalence of BLV infection is approximately 5% in Israel [140], while in Saudi Arabia, 20.2% of dairy cattle tested as BLV-positive [141]. Compared to these countries, BLV infection rates in Turkey are higher, with 48.3% of dairy herds including sero-positive animals [142].

Distribution of BLV genotypes worldwide

As mentioned above, phylogenetic analyses of whole genome (Fig. 3) and env gp51 sequences (Fig. 2) of BLV strain showed that BLV can be classified into ten genotypes. Three genotypes of BLV, namely genotype-1, genotype-4 and genotype-6, were mainly detected from across the world, as shown in Table 4. Genotype-1 is the most dominant genotype of BLV and is distributed across almost all continents, including Europe, America, Asia, and Australia. In particularly, genotype-1 spread to South and North America, and these continents still have a high prevalence of BLV infection. In addition, genotype-1 continues to spread worldwide, including Asian countries. The second most widely distributed genotype is genotype-4, which is primarily detected in Europe and some American countries. However, it is only found in Mongolia among Asian nations. Interestingly, although genotype-4 used to exist in Europe, it decreased because of BLV eradication in European countries. Genotype 6 may have come from South America and spread to South Asia by animal trading. Of the other genotypes, genotype-2 is restricted to South American countries and is only found in Japan among Asian nations, while genotype-8 is restricted to Europe. Genotypes-5 (in Brazil and Costa Rica) and −10 (in Thailand and Myanmar) are only observed in geographically proximal areas, where there may be an exchange of animals across national boundaries [76, 102]. By contrast, genotypes-7 is distributed across geographically dispersed regions [74, 77].
Table 4

Worldwide geographical distribution of the ten known BLV genotypes based on env-gp51 sequences

Geographical division

Country

Genotype

Reference

1

2

3

4

5

6

7

8

9

 

Europe

Belarus

   

4

      

Rola-Luszczak et al., 2013 [99]

Russia

   

4

  

7

8

  

Rola-Luszczak et al., 2013 [99]

Ukraine

   

4

  

7

8

  

Rola-Luszczak et al., 2013 [99]

Croatia

       

8

  

Balic et al., 2012 [97]

Poland

   

4

  

7

   

Rola-Luszczak et al., 2013 [99]

Belgium

   

4

      

Mamoun et al., 1990 [85]; Zhao & Buehring, 2007 [142]

France

  

3

4

      

Mamoun et al., 1990 [85]

Germany

1

  

4

      

Fechner et al., 1997 [90]

Italy

      

7

   

Molteni et al., 1996 [143]

Australia

Australia

1

         

Coulston et al., 1990 [89]

America

USA

1

 

3

4

      

Derse et al., 1985 [144]; Mamoun et al., 1990 [85]; Zhao & Buehring, 2007 [142]

Caribbean

1

         

Yang et al., 2016 [145]

Costa Rica

1

   

5

     

Zhao & Buehring, 2007 [142]

Argentina

1

2

 

4

 

6

    

Dube et al., 2000 [146]; Licursi et al., 2003 [92]; Monti et al., 2005 [94]; Dube et al., 2009 [147]; Rodriguez et al., 2009 [96]

Brazil

1

2

  

5

6

7

   

Camargos et al., 2002 [121]; Camargos et al., 2007 [122]; Moratorio et al., 2010 [126]

Chile

   

4

  

7

   

Felmer et al., 2005 [93]

Bolivia

1

2

   

6

  

9

 

Polat et al., 2016 [75]

Peru

1

2

   

6

    

Polat et al., 2016 [75]

Paraguay

1

2

   

6

    

Polat et al., 2016 [75]

Uruguay

1

         

Moratorio et al., 2010 [126]

Asia

Korea

1

 

3

       

Lim et al., 2009 [148]; Lee et al., 2015 [100]

Japan

1

2

3

       

Licursi et al., 2003 [92]; Zhao & Buehring, 2007 [142]; Matsumura et al., 2011 [98]; Inoue et al., 2011 [149]

Philippines

1

    

6

    

Polat et al., 2015 [74]

Thailand

1

    

6

   

10

Lee et al., 2016 [101]

Myanmar

         

10

Polat et al., 2016 [76]

Mongolia

1

  

4

  

7

   

Ochirkhuu et al., 2016 [77]

Jordan

1

    

6

    

Ababneh et al., 2016 [150]

In detail, in Europe, a total of five different BLV genotypes have been detected (genotypes −1, −3, −4, −7, and −8): genotype-4 in Belarus [100] and Belgium [86, 143]; genotypes-4, −7, and −8 in Russia and Ukraine [100]; genotype-8 in Croatia [98]; genotypes −4 and −7 in Poland [100]; genotypes −3 and −4 in France [86]; genotypes −1 and −4 in Germany [91]; and genotype-7 in Italy [144]. In Australia, only genotype-1 was detected [90]. In North America, genotypes −1, −3, and −4 have been detected in the USA [86, 143, 145], and genotype-1 was reported in the Caribbean [146]. In Central America, genotypes −1 and −5 were detected in Costa Rica [143]. A variety of BLV genotypes (−1, −2, −4, −5, −7, and −9) were detected in South America: genotypes −1, −2, −4, and −6 in Argentina [93, 95, 97, 147, 148]; genotypes −1, −2, −5, −6, and −7 in Brazil [122, 123, 127]; genotypes −4 and −7 in Chile [94]; genotypes −1, −2, −6, and −9 in Bolivia [75]; genotypes −1, −2, and −6 in Peru and Paraguay [75]; and genotype-1 in Uruguay [126]. In Asia, a total of seven BLV genotypes have been confirmed (−1, −2, −3, −4, −6, −7, and −10): genotypes −1 and −3 in Korea [101, 149]; genotypes −1, −2, and −3 in Japan [93, 99, 143, 150]; genotypes −1 and −6 in The Philippines [74]; genotypes −1, −6, and −10 in Thailand [102]; genotypes −1, −4, and −7 in Mongolia [77]; genotype-10 in Myanmar [76]; and genotypes −1 and −6 in Jordan [151].

Based on the European Food Safety Authority panel on animal health and welfare, BLV-induced EBL may have originated and spread widely from an area of Memel in East Prussia (now Klaipeda in Lithuania) [113, 152]. The worldwide distribution of the disease occurred due to the introduction of cattle from European countries into herds in other countries free of the disease, and also through the international trade of bred animals [113]. Interestingly, genotype-4 existed primarily in East Prussia as shown in Table 4. Then, infected cattle were reintroduced into some European countries; for example, BLV was introduced into the UK via bred animals from Canada in 1968 and 1973 [113]. As detailed in some previous publications, the widespread distribution of BLV genotypes within and between distant geographical locations may be driven by the spread of virus through the movement of live animal populations, associated with human migration and animal domestication, and also with viral transmission during close contact between individual animals [97].

Future prospects

It appears that at least ten different BLV genotypes of BLV strains are circulating in various geographical locations worldwide. The completion of whole genome sequencing of these BLV strains has revealed that BLV genomes contain a number of unique genotype specific substitutions not only in the env region, but also in the LTR, Gag, Pro, Pol, Tax, Rex, R3, G4, and miRNA encoding regions, distinguishing each genotype [75]. However, the BLV genome sequences of strains from different geographic origins, especially the important sites on the regulation of viral replication of BLV, are relatively stable and highly conserved among BLV strains, assigned to different genotypes. By contrast, several groups recently reported that the expression or pathogenesis of BLV does not depend on strains, but rather, is related with the specific site of mutation in their BLV genome [153, 154]. These results clearly demonstrate that BLV strain should be determined by full genome sequencing. However, although BLV is present worldwide, BLV genotyping studies are limited to certain areas, as shown in Table 4. Therefore, the accumulation of the full genome sequencing of BLV strains, assigned to different genotypes worldwide may define the genotype-dependent pathogenesis and association between genetic variability in each genotype and its infectivity, and differences in its functions in the future.

Conclusion

BLV is the etiologic agent of EBL, which is the most common neoplastic disease in cattle. It infects cattle worldwide, thereby imposing a severe economic burden on the dairy cattle industry. In this review, we summarized currently available detailed information on BLV infection worldwide, and indicated that BLV has spread to most countries except for some countries which are completely free of BLV by successful BLV eradication. We also outlined at least ten different BLV genotypes circulating in various geographical locations worldwide and the distribution of these BLV genotypes worldwide. This should be useful information to those investigating BLV for the potential development of diagnostic methods and vaccines, and for reducing the incidence of BLV in herds.

Abbreviations

AGID: 

Agar gel immunodiffusion

BI: 

Bayesian inference method

BLV: 

Bovine leukemia virus

EBL: 

Enzootic bovine leukosis

ELISA: 

Enzyme-linked immunosorbent assay

EPAHW: 

European Food Safety Authority panel on animal health and welfare

HTLV-I &-II: 

Human T-cell lymphotropic virus types I and II

LTR: 

Long terminal repeats

miRNA: 

microRNA

ML: 

Maximum likelihood method

NJ: 

Neighbor-joining method

PCR: 

Polymerase chain reaction

PHA: 

Passive hemagglutination assay

PL: 

Persistent lymphocytosis

qPCR: 

Quantitative PCR

RFLP: 

Restriction fragment length polymorphism

RIA: 

Radio immunoassay

STLV: 

Simian T-cell lymphotropic virus

Declarations

Acknowledgments

We thank our collaborators for kindly assisting with the large-scale sampling from many farms in the Philippine, Myanmar, South America (Argentina, Peru, Paraguay, Chile and Bolivia) and Japan.

Funding

The studies on BLV were supported by Grants-in-Aid for Scientific Research [A (08021470), A (16H02590), B (10004294), and C (25450405)] from the Japan Society for the Promotion of Science (JSPS), by a grant from Integration Research for Agriculture and Interdisciplinary Fields in Japan (14538311), and by a grant from the Project of the NARO Bio-oriented Technology Research Advancement Institution (the special scheme project on regional developing strategy) (Grant No. 16817983)].

Availability of data and materials

Not applicable

Authors’ contributions

Yoko Aida designed the concept of the review article, edited and revised the manuscript. Meripet Polat wrote the manuscript, constructed Tables and Figures, and edited and revised the manuscript. Shin-nosuke Takeshima wrote some part and helped with the revision of the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Viral Infectious Diseases Unit, RIKEN
(2)
Nano Medical Engineering Laboratory, RIKEN
(3)
Bovine Leukemia Virus Vaccine Laboratory RIKEN

References

  1. Kettmann R, Portetelle D, Mammerickx M, Cleuter Y, Dekegel D, Galoux M, Ghysdael J, Burny A, Chantrenne H. Bovine leukemia virus: an exogenous RNA oncogenic virus. Proc Natl Acad Sci U S A. 1976;73:1014–8.PubMedPubMed CentralView ArticleGoogle Scholar
  2. Aida Y, Murakami H, Takahashi M, Takeshima SN. Mechanisms of pathogenesis induced by bovine leukemia virus as a model for human T-cell leukemia virus. Front Microbiol. 2013;4:328.PubMedPubMed CentralView ArticleGoogle Scholar
  3. Tozser J. Comparative studies on retroviral proteases: substrate specificity. Viruses. 2010;2:147–65.PubMedPubMed CentralView ArticleGoogle Scholar
  4. Hajj HE, Nasr R, Kfoury Y, Dassouki Z, Nasser R, Kchour G, Hermine O, De The H, Bazarbachi A. Animal models on HTLV-1 and related viruses: what did we learn? Front Microbiol. 2012;3:333.PubMedPubMed CentralView ArticleGoogle Scholar
  5. Kirkland PD, Rodwell BJ. Enzootic Bovine Leukosis. Australia and New Zealand Standard Diagnostic Procedures. 2005:1–14.Google Scholar
  6. Williams DL, Barta O, Amborski GF. Molecular studies of T-lymphocytes from cattle infected with bovine leukemia virus. Vet Immunol Immunopathol. 1988;19:307–23.PubMedView ArticleGoogle Scholar
  7. Stott ML, Thurmond MC, Dunn SJ, Osburn BI, Stott JL. Integrated bovine leukosis proviral DNA in T helper and T cytotoxic/suppressor lymphocytes. J Gen Virol. 1991;72(Pt 2):307–15.PubMedView ArticleGoogle Scholar
  8. Schwartz I, Bensaid A, Polack B, Perrin B, Berthelemy M, Levy D. In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. J Virol. 1994;68:4589–96.PubMedPubMed CentralGoogle Scholar
  9. Mirsky ML, Olmstead CA, Da Y, Lewin HA. The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection. J Virol. 1996;70:2178–83.PubMedPubMed CentralGoogle Scholar
  10. Wu D, Takahashi K, Murakami K, Tani K, Koguchi A, Asahina M, Goryo M, Aida Y, Okada K. B-1a, B-1b and conventional B cell lymphoma from enzootic bovine leukosis. Vet Immunol Immunopathol. 1996;55:63–72.PubMedView ArticleGoogle Scholar
  11. Panei CJ, Takeshima SN, Omori T, Nunoya T, Davis WC, Ishizaki H, Matoba K, Aida Y. Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR. BMC Vet Res. 2013;9:95.PubMedPubMed CentralView ArticleGoogle Scholar
  12. Aida Y, Okada K, Amanuma H. Phenotype and ontogeny of cells carrying a tumor-associated antigen that is expressed on bovine leukemia virus-induced lymphosarcoma. Cancer Res. 1993;53:429–37.PubMedGoogle Scholar
  13. Nekouei O, VanLeeuwen J, Stryhn H, Kelton D, Keefe G. Lifetime effects of infection with bovine leukemia virus on longevity and milk production of dairy cows. Prev Vet Med. 2016;133:1–9.PubMedView ArticleGoogle Scholar
  14. Sandev N, Koleva M, Binev R, Ilieva D. Influence of enzootic bovine leukosis virus upon the incidence of subclinical mastitis in cows at a different stage of infection. Veterinarski Archiv. 2004;76:411–6.Google Scholar
  15. Bartlett PC, Norby B, Byrem TM, Parmelee A, Ledergerber JT, Erskine RJ. Bovine leukemia virus and cow longevity in Michigan dairy herds. J Dairy Sci. 2013;96:1591–7.PubMedView ArticleGoogle Scholar
  16. Ferrer JF, Marshak RR, Abt DA, Kenyon SJ. Persistent lymphocytosis in cattle: its cause, nature and relation to lymphosarcoma. Ann Rech Vet. 1978;9:851–7.PubMedGoogle Scholar
  17. OIE. Manual of diagnostic tests and vaccines for terrestrial animals: chapter 2.4.11. Enzootic Bovine Leukosis. Seventh Edition edn. France: World organization for animal health; 2012.Google Scholar
  18. Sagata N, Yasunaga T, Tsuzuku-Kawamura J, Ohishi K, Ogawa Y, Ikawa Y. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc Natl Acad Sci U S A. 1985;82:677–81.PubMedPubMed CentralView ArticleGoogle Scholar
  19. Sagata N, Yasunaga T, Ohishi K, Tsuzuku-Kawamura J, Onuma M, Ikawa Y. Comparison of the entire genomes of bovine leukemia virus and human T-cell leukemia virus and characterization of their unidentified open reading frames. EMBO J. 1984;3:3231–7.PubMedPubMed CentralGoogle Scholar
  20. Callebaut I, Voneche V, Mager A, Fumiere O, Krchnak V, Merza M, Zavada J, Mammerickx M, Burny A, Portetelle D. Mapping of B-neutralizing and T-helper cell epitopes on the bovine leukemia virus external glycoprotein gp51. J Virol. 1993;67:5321–7.PubMedPubMed CentralGoogle Scholar
  21. Inabe K, Nishizawa M, Tajima S, Ikuta K, Aida Y. The YXXL sequences of a transmembrane protein of bovine leukemia virus are required for viral entry and incorporation of viral envelope protein into virions. J Virol. 1999;73:1293–301.PubMedPubMed CentralGoogle Scholar
  22. Jewell NA, Mansky LM. The beginning: genome recognition, RNA encapsidation and the initiation of complex retrovirus assembly. J Gen Virol. 2000;81:1889–99.PubMedView ArticleGoogle Scholar
  23. Hamard-Peron E, Muriaux D. Retroviral matrix and lipids, the intimate interaction. Retrovirology. 2011;8:15.PubMedPubMed CentralView ArticleGoogle Scholar
  24. Bai L, Otsuki H, Sato H, Kohara J, Isogai E, Takeshima SN, Aida Y. Identification and characterization of common B cell epitope in bovine leukemia virus via high-throughput peptide screening system in infected cattle. Retrovirology. 2015;12:106.PubMedPubMed CentralView ArticleGoogle Scholar
  25. Copeland TD, Morgan MA, Oroszlan S. Complete amino acid sequence of the nucleic acid-binding protein of bovine leukemia virus. FEBS Lett. 1983;156:37–40.PubMedView ArticleGoogle Scholar
  26. Mager A, Masengo R, Mammerickx M, Letesson JJ. T cell proliferative response to bovine leukaemia virus (BLV): identification of T cell epitopes on the major core protein (p24) in BLV-infected cattle with normal haematological values. J Gen Virol. 1994;75(Pt 9):2223–31.PubMedView ArticleGoogle Scholar
  27. Willems L, Kerkhofs P, Attenelle L, Burny A, Portetelle D, Kettmann R. The major homology region of bovine leukaemia virus p24gag is required for virus infectivity in vivo. J Gen Virol. 1997;78(Pt 3):637–40.PubMedView ArticleGoogle Scholar
  28. Katoh I, Yasunaga T, Yoshinaka Y. Bovine leukemia virus RNA sequences involved in dimerization and specific gag protein binding: close relation to the packaging sites of avian, murine, and human retroviruses. J Virol. 1993;67:1830–9.PubMedPubMed CentralGoogle Scholar
  29. Willems L, Heremans H, Chen G, Portetelle D, Billiau A, Burny A, Kettmann R. Cooperation between bovine leukaemia virus transactivator protein and ha-ras oncogene product in cellular transformation. EMBO J. 1990;9:1577–81.PubMedPubMed CentralGoogle Scholar
  30. Willems L, Grimonpont C, Heremans H, Rebeyrotte N, Chen G, Portetelle D, Burny A, Kettmann R. Mutations in the bovine leukemia-virus tax protein can abrogate the long terminal repeat-directed Transactivating activity without concomitant loss of transforming potential. Proc Natl Acad Sci U S A. 1992;89:3957–61.PubMedPubMed CentralView ArticleGoogle Scholar
  31. Tajima S, Aida Y. The region between amino acids 245 and 265 of the bovine leukemia virus (BLV) tax protein restricts transactivation not only via the BLV enhancer but also via other retrovirus enhancers. J Virol. 2000;74:10939–49.PubMedPubMed CentralView ArticleGoogle Scholar
  32. Felber BK, Derse D, Athanassopoulos A, Campbell M, Pavlakis GN. Cross-activation of the Rex proteins of HTLV-I and BLV and of the rev protein of HIV-1 and nonreciprocal interactions with their RNA responsive elements. New Biol. 1989;1:318–28.PubMedGoogle Scholar
  33. Tajima S, Takahashi M, Takeshima SN, Konnai S, Yin SA, Watarai S, Tanaka Y, Onuma M, Okada K, Aida Y. A mutant form of the tax protein of bovine leukemia virus (BLV), with enhanced transactivation activity, increases expression and propagation of BLV in vitro but not in vivo. J Virol. 2003;77:1894–903.PubMedPubMed CentralView ArticleGoogle Scholar
  34. Takahashi M, Tajima S, Takeshima SN, Konnai S, Yin SA, Okada K, Davis WC, Aida Y. Ex vivo survival of peripheral blood mononuclear cells in sheep induced by bovine leukemia virus (BLV) mainly occurs in CD5- B cells that express BLV. Microbes Infect. 2004;6:584–95.PubMedView ArticleGoogle Scholar
  35. Takahashi M, Tajima S, Okada K, Davis WC, Aida Y. Involvement of bovine leukemia virus in induction and inhibition of apoptosis. Microbes Infect. 2005;7:19–28.PubMedView ArticleGoogle Scholar
  36. Tajima S, Aida Y. Mutant tax protein from bovine leukemia virus with enhanced ability to activate the expression of c-fos. J Virol. 2002;76:2557–62.PubMedPubMed CentralView ArticleGoogle Scholar
  37. Willems L, Kerkhofs P, Dequiedt F, Portetelle D, Mammerickx M, Burny A, Kettmann R. Attenuation of bovine leukemia virus by deletion of R3 and G4 open reading frames. Proc Natl Acad Sci U S A. 1994;91:11532–6.PubMedPubMed CentralView ArticleGoogle Scholar
  38. Florins A, Gillet N, Boxus M, Kerkhofs P, Kettmann R, Willems L. Even attenuated bovine leukemia virus proviruses can be pathogenic in sheep. J Virol. 2007;81:10195–200.PubMedPubMed CentralView ArticleGoogle Scholar
  39. Kincaid RP, Burke JM, Sullivan CS. RNA virus microRNA that mimics a B-cell oncomiR. Proc Natl Acad Sci U S A. 2012;109:3077–82.PubMedPubMed CentralView ArticleGoogle Scholar
  40. Rosewick N, Momont M, Durkin K, Takeda H, Caiment F, Cleuter Y, Vernin C, Mortreux F, Wattel E, Burny A, et al. Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma. Proc Natl Acad Sci U S A. 2013;110:2306–11.PubMedPubMed CentralView ArticleGoogle Scholar
  41. Gillet NA, Hamaidia M, de Brogniez A, Gutierrez G, Renotte N, Reichert M, Trono K, Willems L. Bovine leukemia virus small noncoding RNAs are functional elements that regulate replication and contribute to Oncogenesis in vivo. PLoS Pathog. 2016;12:e1005588.PubMedPubMed CentralView ArticleGoogle Scholar
  42. Van Driessche B, Rodari A, Delacourt N, Fauquenoy S, Vanhulle C, Burny A, Rohr O, Van Lint C. Characterization of new RNA polymerase III and RNA polymerase II transcriptional promoters in the bovine leukemia virus genome. Sci Rep. 2016;6:31125.PubMedPubMed CentralView ArticleGoogle Scholar
  43. Jimba M, Takeshima SN, Murakami H, Kohara J, Kobayashi N, Matsuhashi T, Ohmori T, Nunoya T, Aida Y. BLV-CoCoMo-qPCR: a useful tool for evaluating bovine leukemia virus infection status. BMC Vet Res. 2012;8:167.PubMedPubMed CentralView ArticleGoogle Scholar
  44. Walker PJ, Molloy JB, Rodwell BJ. A protein immunoblot test for detection of bovine leukemia virus p24 antibody in cattle and experimentally infected sheep. J Virol Methods. 1987;15:201–11.PubMedView ArticleGoogle Scholar
  45. Portetelle D, Bruck C, Mammerickx M, Burny A. In animals infected by bovine leukemia virus (BLV) antibodies to envelope glycoprotein gp51 are directed against the carbohydrate moiety. Virology. 1980;105:223–33.PubMedView ArticleGoogle Scholar
  46. Bai L, Takeshima SN, Isogai E, Kohara J, Aida Y. Novel CD8(+) cytotoxic T cell epitopes in bovine leukemia virus with cattle. Vaccine. 2015;33:7194–202.PubMedView ArticleGoogle Scholar
  47. Aida Y, Miyasaka M, Okada K, Onuma M, Kogure S, Suzuki M, Minoprio P, Levy D, Ikawa Y. Further phenotypic characterization of target cells for bovine leukemia virus experimental infection in sheep. Am J Vet Res. 1989;50:1946–51.PubMedGoogle Scholar
  48. Wang CT. Bovine leukemia virus infection in Taiwan: epidemiological study. J Vet Med Sci. 1991;53:395–8.PubMedView ArticleGoogle Scholar
  49. Monti GE, Frankena K, Engel B, Buist W, Tarabla HD, de Jong MC. Evaluation of a new antibody-based enzyme-linked immunosorbent assay for the detection of bovine leukemia virus infection in dairy cattle. J Vet Diagn Investig. 2005;17:451–7.View ArticleGoogle Scholar
  50. Kurdi A, Blankenstein P, Marquardt O, Ebner D. Serologic and virologic investigations on the presence of BLV infection in a dairy herd in Syria. Berl Munch Tierarztl Wochenschr. 1999;112:18–23.PubMedGoogle Scholar
  51. Fukai K, Sato M, Kawara M, Hoshi Z, Ueno S, Chyou N, Akashi H. A case of an embryo transfer calf infected with bovine leukemia virus from the recipient cow. Zentralbl Veterinarmed B. 1999;46:511–5.PubMedGoogle Scholar
  52. Zaghawa A, Beier D, Abd El-Rahim IH, Karim I, El-ballal S, Conraths FJ, Marquardt O. An outbreak of enzootic bovine leukosis in upper Egypt: clinical, laboratory and molecular-epidemiological studies. J Vet Med B Infect Dis Vet Public Health. 2002;49:123–9.PubMedView ArticleGoogle Scholar
  53. Schoepf KC, Kapaga AM, Msami HM, Hyera JM. Serological evidence of the occurrence of enzootic bovine leukosis (EBL) virus infection in cattle in Tanzania. Trop Anim Health Prod. 1997;29:15–9.PubMedView ArticleGoogle Scholar
  54. Levy D, Deshayes L, Parodi AL, Levy JP, Stephenson JR, Devare SG, Gilden RV. Bovine leukemia virus specific antibodies among French cattle. II. Radioimmunoassay with the major structural protein (BLV p24). Int J Cancer. 1977;20:543–50.PubMedView ArticleGoogle Scholar
  55. Naif HM, Brandon RB, Daniel RCW, Lavin MF. Bovine leukemia Proviral DNA detection in cattle using the polymerase chain-reaction. Vet Microbiol. 1990;25:117–29.PubMedView ArticleGoogle Scholar
  56. Burridge MJ, Thurmond MC, Miller JM, Schmerr MJ, Van Der Maaten MJ. Fall in antibody titer to bovine leukemia virus in the periparturient period. Can J Comp Med. 1982;46:270–1.PubMedPubMed CentralGoogle Scholar
  57. Nguyen VK, Maes RF. Evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to bovine leukemia virus in serum and milk. J Clin Microbiol. 1993;31:979–81.PubMedPubMed CentralGoogle Scholar
  58. Ohshima K, Morimoto N, Kagawa Y, Numakunai S, Hirano T, Kayano HA. Survey for maternal antibodies to bovine leukemia virus (BLV) in calves born to cows infected with BLV. Nihon Juigaku Zasshi. 1984;46:583–6.PubMedView ArticleGoogle Scholar
  59. Kettmann R, Meunier-Rotival M, Cortadas J, Cuny G, Ghysdael J, Mammerickx M, Burny A, Bernardi G. Integration of bovine leukemia virus DNA in the bovine genome. Proc Natl Acad Sci U S A. 1979;76:4822–6.PubMedPubMed CentralView ArticleGoogle Scholar
  60. Kettmann R, Deschamps J, Cleuter Y, Couez D, Burny A, Marbaix G. Leukemogenesis by bovine leukemia virus: proviral DNA integration and lack of RNA expression of viral long terminal repeat and 3′ proximate cellular sequences. Proc Natl Acad Sci U S A. 1982;79:2465–9.PubMedPubMed CentralView ArticleGoogle Scholar
  61. Tajima S, Tsukamoto M, Aida Y. Latency of viral expression in vivo is not related to CpG methylation in the U3 region and part of the R region of the long terminal repeat of bovine leukemia virus. J Virol. 2003;77:4423–30.PubMedPubMed CentralView ArticleGoogle Scholar
  62. Tajima S, Aida Y. Induction of expression of bovine leukemia virus (BLV) in blood taken from BLV-infected cows without removal of plasma. Microbes Infect. 2005;7:1211–6.PubMedView ArticleGoogle Scholar
  63. Kettmann R, Cleuter Y, Mammerickx M, Meunier-Rotival M, Bernardi G, Burny A, Chantrenne H. Genomic integration of bovine leukemia provirus: comparison of persistent lymphocytosis with lymph node tumor form of enzootic. Proc Natl Acad Sci U S A. 1980;77:2577–81.PubMedPubMed CentralView ArticleGoogle Scholar
  64. Tajima S, Ikawa Y, Aida Y. Complete bovine leukemia virus (BLV) provirus is conserved in BLV-infected cattle throughout the course of B-cell lymphosarcoma development. J Virol. 1998;72:7569–76.PubMedPubMed CentralGoogle Scholar
  65. Burny A, Cleuter Y, Kettmann R, Mammerickx M, Marbaix G, Portetelle D, Vandenbroeke A, Willems L, Thomas R. Bovine leukemia - facts and hypotheses derived from the study of an infectious cancer. Vet Microbiol. 1988;17:197–218.PubMedView ArticleGoogle Scholar
  66. Brym P, Rusc A, Kaminski S. Evaluation of reference genes for qRT-PCR gene expression studies in whole blood samples from healthy and leukemia-virus infected cattle. Vet Immunol Immunopathol. 2013;153:302–7.PubMedView ArticleGoogle Scholar
  67. Tawfeeq MM, Horiuchi N, Kobayashi Y, Furuoka H, Inokuma H. Evaluation of gene expression in peripheral blood cells as a potential biomarker for enzootic bovine Leukosis. J Vet Med Sci. 2013;75:1213–7.PubMedView ArticleGoogle Scholar
  68. Somura Y, Sugiyama E, Fujikawa H, Murakami K. Comparison of the copy numbers of bovine leukemia virus in the lymph nodes of cattle with enzootic bovine leukosis and cattle with latent infection. Arch Virol. 2014;159:2693–7.PubMedView ArticleGoogle Scholar
  69. Lew AE, Bock RE, Miles J, Cuttell LB, Steer P, Nadin-Davis SA. Sensitive and specific detection of bovine immunodeficiency virus and bovine syncytial virus by 5’Taq nuclease assays with fluorescent 3’minor groove binder-DNA probes. J Virol Methods. 2004;116:1–9.PubMedView ArticleGoogle Scholar
  70. Jimba M, Takeshima SN, Matoba K, Endoh D, Aida Y. BLV-CoCoMo-qPCR: Quantitation of bovine leukemia virus proviral load using the CoCoMo algorithm. Retrovirology. 2010;7:91.PubMedPubMed CentralView ArticleGoogle Scholar
  71. Takeshima SN, Kitamura-Muramatsu Y, Yuan Y, Polat M, Saito S, Aida Y. BLV-CoCoMo-qPCR-2: improvements to the BLV-CoCoMo-qPCR assay for bovine leukemia virus by reducing primer degeneracy and constructing an optimal standard curve. Arch Virol. 2015;160:1325–32.PubMedView ArticleGoogle Scholar
  72. Nishimori A, Konnai S, Ikebuchi R, Okagawa T, Nakahara A, Murata S, Ohashi K. Direct polymerase chain reaction from blood and tissue samples for rapid diagnosis of bovine leukemia virus infection. J Vet Med Sci. 2016;78:791–6.PubMedPubMed CentralView ArticleGoogle Scholar
  73. Takeshima SN, Watanuki S, Ishizaki H, Matoba K, Aida Y. Development of a direct blood-based PCR system to detect BLV provirus using CoCoMo primers. Arch Virol. 2016;161:1539–46.PubMedView ArticleGoogle Scholar
  74. Polat M, Ohno A, Takeshima SN, Kim J, Kikuya M, Matsumoto Y, Mingala CN, Onuma M, Aida Y. Detection and molecular characterization of bovine leukemia virus in Philippine cattle. Arch Virol. 2015;160:285–96.PubMedView ArticleGoogle Scholar
  75. Polat M, Takeshima SN, Hosomichi K, Kim J, Miyasaka T, Yamada K, Arainga M, Murakami T, Matsumoto Y, de la Barra Diaz V, et al. A new genotype of bovine leukemia virus in South America identified by NGS-based whole genome sequencing and molecular evolutionary genetic analysis. Retrovirology. 2016;13:4.PubMedPubMed CentralView ArticleGoogle Scholar
  76. Polat M, Moe HH, Shimogiri T, Moe KK, Takeshima SN, Aida Y. The molecular epidemiological study of bovine leukemia virus infection in Myanmar cattle. Arch Virol. 2016.Google Scholar
  77. Ochirkhuu N, Konnai S, Odbileg R, Nishimori A, Okagawa T, Murata S, Ohashi K. Detection of bovine leukemia virus and identification of its genotype in Mongolian cattle. Arch Virol. 2016;161:985–91.PubMedView ArticleGoogle Scholar
  78. Dus Santos MJ, Trono K, Lager I, Wigdorovitz A. Development of a PCR to diagnose BLV genome in frozen semen samples. Vet Microbiol. 2007;119:10–8.PubMedView ArticleGoogle Scholar
  79. Martin D, Arjona A, Soto I, Barquero N, Viana M, Gomez-Lucia E. Comparative study of PCR as a direct assay and ELISA and AGID as indirect assays for the detection of bovine leukaemia virus. J Vet Med B Infect Dis Vet Public Health. 2001;48:97–106.PubMedView ArticleGoogle Scholar
  80. Heenemann K, Lapp S, Teifke JP, Fichtner D, Mettenleiter TC, Vahlenkamp TW. Development of a bovine leukemia virus polymerase gene-based real-time polymerase chain reaction and comparison with an envelope gene-based assay. J Vet Diagn Investig. 2012;24:649–55.View ArticleGoogle Scholar
  81. Kelly EJ, Jackson MK, Marsolais G, Morrey JD, Callan RJ. Early detection of bovine leukemia virus in cattle by use of the polymerase chain reaction. Am J Vet Res. 1993;54:205–9.PubMedGoogle Scholar
  82. Miyasaka T, Takeshima SN, Jimba M, Matsumoto Y, Kobayashi N, Matsuhashi T, Sentsui H, Aida Y. Identification of bovine leukocyte antigen class II haplotypes associated with variations in bovine leukemia virus proviral load in Japanese black cattle. Tissue Antigens. 2013;81:72–82.PubMedView ArticleGoogle Scholar
  83. Ohno A, Takeshima SN, Matsumoto Y, Aida Y. Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014. Virus Res. 2015;210:283–90.PubMedView ArticleGoogle Scholar
  84. Yuan Y, Kitamura-Muramatsu Y, Saito S, Ishizaki H, Nakano M, Haga S, Matoba K, Ohno A, Murakami H, Takeshima SN, Aida Y. Detection of the BLV provirus from nasal secretion and saliva samples using BLV-CoCoMo-qPCR-2: comparison with blood samples from the same cattle. Virus Res. 2015;210:248–54.PubMedView ArticleGoogle Scholar
  85. Inabe K, Ikuta K, Aida Y. Transmission and propagation in cell culture of virus produced by cells transfected with an infectious molecular clone of bovine leukemia virus. Virology. 1998;245:53–64.PubMedView ArticleGoogle Scholar
  86. Mamoun RZ, Morisson M, Rebeyrotte N, Busetta B, Couez D, Kettmann R, Hospital M, Guillemain B. Sequence variability of bovine leukemia virus env gene and its relevance to the structure and antigenicity of the glycoproteins. J Virol. 1990;64:4180–8.PubMedPubMed CentralGoogle Scholar
  87. Portetelle D, Couez D, Bruck C, Kettmann R, Mammerickx M, Van der Maaten M, Brasseur R, Burny A. Antigenic variants of bovine leukemia virus (BLV) are defined by amino acid substitutions in the NH2 part of the envelope glycoprotein gp51. Virology 1989; 169:27-33.Google Scholar
  88. Bruck C, Mathot S, Portetelle D, Berte C, Franssen JD, Herion P, Burny A. Monoclonal antibodies define eight independent antigenic regions on the bovine leukemia virus (BLV) envelope glycoprotein gp51. Virology. 1982;122:342–52.PubMedView ArticleGoogle Scholar
  89. Kettmann R, Couez D, Burny A. Restriction endonuclease mapping of linear unintegrated proviral DNA of bovine leukemia virus. J Virol. 1981;38:27–33.PubMedPubMed CentralGoogle Scholar
  90. Coulston J, Naif H, Brandon R, Kumar S, Khan S, Daniel RC, Lavin MF. Molecular cloning and sequencing of an Australian isolate of proviral bovine leukaemia virus DNA: comparison with other isolates. J Gen Virol. 1990;71:1737–46.PubMedView ArticleGoogle Scholar
  91. Fechner H, Blankenstein P, Looman AC, Elwert J, Geue L, Albrecht C, Kurg A, Beier D, Marquardt O, Ebner D. Provirus variants of the bovine leukemia virus and their relation to the serological status of naturally infected cattle. Virology. 1997;237:261–9.PubMedView ArticleGoogle Scholar
  92. Licursi M, Inoshima Y, Wu D, Yokoyama T, Gonzalez ET, Sentsui H. Genetic heterogeneity among bovine leukemia virus genotypes and its relation to humoral responses in hosts. Virus Res. 2002;86:101–10.PubMedView ArticleGoogle Scholar
  93. Licursi M, Inoshima Y, Wu D, Yokoyama T, Gonzalez ET, Sentsui H. Provirus variants of bovine leukemia virus in naturally infected cattle from Argentina and Japan. Vet Microbiol. 2003;96:17–23.PubMedView ArticleGoogle Scholar
  94. Felmer R, Munoz G, Zuniga J, Recabal M. Molecular analysis of a 444 bp fragment of the bovine leukaemia virus gp51 env gene reveals a high frequency of non-silent point mutations and suggests the presence of two subgroups of BLV in Chile. Vet Microbiol. 2005;108:39–47.PubMedView ArticleGoogle Scholar
  95. Monti G, Schrijver R, Beier D. Genetic diversity and spread of bovine leukaemia virus isolates in argentine dairy cattle. Arch Virol. 2005;150:443–58.PubMedView ArticleGoogle Scholar
  96. Asfaw Y, Tsuduku S, Konishi M, Murakami K, Tsuboi T, Wu D, Sentsui H. Distribution and superinfection of bovine leukemia virus genotypes in Japan. Arch Virol. 2005;150:493–505.PubMedView ArticleGoogle Scholar
  97. Rodriguez SM, Golemba MD, Campos RH, Trono K, Jones LR. Bovine leukemia virus can be classified into seven genotypes: evidence for the existence of two novel clades. J Gen Virol. 2009;90:2788–97.PubMedView ArticleGoogle Scholar
  98. Balic D, Lojkic I, Periskic M, Bedekovic T, Jungic A, Lemo N, Roic B, Cac Z, Barbic L, Madic J. Identification of a new genotype of bovine leukemia virus. Arch Virol. 2012;157:1281–90.PubMedView ArticleGoogle Scholar
  99. Matsumura K, Inoue E, Osawa Y, Okazaki K. Molecular epidemiology of bovine leukemia virus associated with enzootic bovine leukosis in Japan. Virus Res. 2011;155:343–8.PubMedView ArticleGoogle Scholar
  100. Rola-Luszczak M, Pluta A, Olech M, Donnik I, Petropavlovskiy M, Gerilovych A, Vinogradova I, Choudhury B, Kuzmak J. The molecular characterization of bovine leukaemia virus isolates from Eastern Europe and Siberia and its impact on phylogeny. PLoS One. 2013;8:e58705.PubMedPubMed CentralView ArticleGoogle Scholar
  101. Lee E, Kim EJ, Joung HK, Kim BH, Song JY, Cho IS, Lee KK, Shin YK. Sequencing and phylogenetic analysis of the gp51 gene from Korean bovine leukemia virus isolates. Virol J. 2015;12:64.PubMedPubMed CentralView ArticleGoogle Scholar
  102. Lee E, Kim EJ, Ratthanophart J, Vitoonpong R, Kim BH, Cho IS, Song JY, Lee KK, Shin YK. Molecular epidemiological and serological studies of bovine leukemia virus (BLV) infection in Thailand cattle. Infect Genet Evol. 2016;41:245–54.PubMedView ArticleGoogle Scholar
  103. OIE. World animal health infromation database-version: 1.4. Paris France: World organisation for animal Health; 2009.Google Scholar
  104. Nuotio L, Rusanen H, Sihvonen L, Neuvonen E. Eradication of enzootic bovine leukosis from Finland. Prev Vet Med. 2003;59:43–9.PubMedView ArticleGoogle Scholar
  105. Acaite J, Tamosiunas V, Lukauskas K, Milius J, Pieskus J. The eradication experience of enzootic bovine leukosis from Lithuania. Prev Vet Med. 2007;82:83–9.PubMedView ArticleGoogle Scholar
  106. Kautzsch S, Schluter H. Prognosis and economic-aspects relating to control of enzootic bovine Leukosis. Monatsh Veterinarmed 1990; 45:41-45.Google Scholar
  107. Maresca C, Costarelli S, Dettori A, Felici A, Iscaro C, Feliziani F. Enzootic bovine leukosis: report of eradication and surveillance measures in Italy over an 8-year period (2005-2012). Prev Vet Med. 2015;119:222–6.PubMedView ArticleGoogle Scholar
  108. Gottschau A, Willeberg P, Franti CE, Flensburg JC. The effect of a control program for enzootic bovine leukosis. Changes in herd prevalence in Denmark, 1969-1978. Am J Epidemiol. 1990;131:356–64.PubMedView ArticleGoogle Scholar
  109. Stark KD. Animal health monitoring and surveillance in Switzerland. Aust Vet J. 1996;73:96–7.PubMedView ArticleGoogle Scholar
  110. EFSA Panel on Animal Health and Welfare, More SJ, Bøtner A, Butterworth A, Calistri P, Depner K, Bicout D. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): enzootic bovine leukosis (EBL). EFSA J. 2017;15(8):1–28.Google Scholar
  111. Zhao XR, Jimenez C, Sentsui H, Buehring GC. Sequence polymorphisms in the long terminal repeat of bovine leukemia virus: evidence for selection pressures in regulatory sequences. Virus Res 2007; 124:113–124.Google Scholar
  112. Sandev N, Illieva D, Rusenova N, Marasheva V. Prevalence of enzootic Bobivne Leukosis in Bulgaria. Bulletin UASVM Veterinary Medicine. 2015;72:43–6.Google Scholar
  113. European Panal on Animal Health and Welfare (EPAHW). Scientific opinion on enzootic bovine leukosis. EFSA J. 2015;13:63.Google Scholar
  114. Chethanond U-S. The epidemiology of enzootic bovine leukosis in diary cattle in New Zealand. Massey University; 1999.Google Scholar
  115. APHIS. Bovine Leukosis Virus (BLV) on U.S.Dairy Operations, 2007. United states department of agriculture; 2008.Google Scholar
  116. VanLeeuwen JA, Keefe GP, Tremblay R, Power C, Wichtel JJ. Seroprevalence of infection with Mycobacterium Avium subspecies paratuberculosis, bovine leukemia virus, and bovine viral diarrhea virus in maritime Canada dairy cattle. Can Vet J. 2001;42:193–8.PubMedPubMed CentralGoogle Scholar
  117. VanLeeuwen JA, Forsythe L, Tiwari A, Chartier R. Seroprevalence of antibodies against bovine leukemia virus, bovine viral diarrhea virus, Mycobacterium Avium subspecies paratuberculosis, and Neospora caninum in dairy cattle in Saskatchewan. Can Vet J. 2005;46:56–8.PubMedPubMed CentralGoogle Scholar
  118. Nekouei OA. Study of prevalence, risk factors, and lifetime impacts of infection with bovine keukemia virus in the Canadian dairy industry. University of Prince Edward Island, Atlanti veterinary college, department of. Health Management. 2015;Google Scholar
  119. Suzan VM, Onuma M, Aguilar RE, Murakami Y. Prevalence of bovine Herpesvirus-1, Para-Influenza-3, bovine rotavirus, bovine viral diarrhea, bovine Adenovirus-7, bovine leukemia-virus and bluetongue virus-antibodies in cattle in Mexico. Jap J Vet Res. 1983;31:125–32.Google Scholar
  120. Samara SI, Lima EG, Nascimento AA. Monitoring of enzootic bovine leukosis in dairy cattle from the Pitangueiras region in São Paulo, Brazil. Braz J Vet Res Anim Sci. 1997;34:349–51.View ArticleGoogle Scholar
  121. D'Angelino JL, Garcia M, Birgel EH. Epidemiological study of enzootic bovine leukosis in Brazil. Trop Anim Health Prod. 1998;30:13–5.PubMedView ArticleGoogle Scholar
  122. Camargos MF, Stancek D, Rocha MA, Lessa LM, Reis JK, Leite RC. Partial sequencing of env gene of bovine leukaemia virus from Brazilian samples and phylogenetic analysis. J Vet Med B Infect Dis Vet Public Health. 2002;49:325–31.PubMedView ArticleGoogle Scholar
  123. Camargos MF, Pereda A, Stancek D, Rocha MA, dos Reis JK, Greiser-Wilke I, Leite RC. Molecular characterization of the env gene from Brazilian field isolates of bovine leukemia virus. Virus Genes. 2007;34:343–50.PubMedView ArticleGoogle Scholar
  124. Trono KG, Perez-Filgueira DM, Duffy S, Borca MV, Carrillo C. Seroprevalence of bovine leukemia virus in dairy cattle in Argentina: comparison of sensitivity and specificity of different detection methods. Vet Microbiol. 2001;83:235–48.PubMedView ArticleGoogle Scholar
  125. Bovine CAH. Leukaemia virus infection in Peru. Trop Anim Health Prod. 1983;15:61.View ArticleGoogle Scholar
  126. Marín C, de López NM, Alvarez L, Lozano O, España W, Castaños H, León A. Epidemiology of bovine leukemia in Venezuela. Ann Rech Vet. 1978;9:4.Google Scholar
  127. Moratorio G, Obal G, Dubra A, Correa A, Bianchi S, Buschiazzo A, Cristina J, Pritsch O. Phylogenetic analysis of bovine leukemia viruses isolated in South America reveals diversification in seven distinct genotypes. Arch Virol. 2010;155:481–9.PubMedView ArticleGoogle Scholar
  128. Rama G, Moratorio G, Greif G, Obal G, Bianchi S, Tomé L, Carrion F, Meikle A, Pritsch O. Development of a real time PCR assay using SYBR Green chemistry for bovine leukemia virus detection. Retrovirology. 2011: 8.Google Scholar
  129. Alfonso R, Almansa JE, Barrera JD. Serological prevalence and evaluation of risk factors of enzootic bovine leukosis in the Sabana de Bogota region and the Ubate and Chiquinquira valleys of Colombia. Revue Scientifique Et Technique De L Office International Des Epizooties. 1998;17:723–32.View ArticleGoogle Scholar
  130. Hernández-Herrera DY, Posso-Terranova A, Benavides J, Muñoz-Flórez J, Giovambattista G, Álvarez-Franco L. Bovine leukosis virus detection in Creole Colombian breeds using nested-PCR. ACTA AGRONÓMICA. 2011;60:311–7.Google Scholar
  131. Benavides B, Quevedo D, Cruz M. Epidemiological study of bovine leukemia virus in dairy cows in six herds in the municipality of Pasto Nariño. Revista Lasallista de Investigación. 2013;10:18–26.Google Scholar
  132. Yang Y, Fan W, Mao Y, Yang Z, Lu G, Zhang R, Zhang H, Szeto C, Wang C. Bovine leukemia virus infection in cattle of China: association with reduced milk production and increased somatic cell score. J Dairy Sci. 2016;99:3688–97.PubMedView ArticleGoogle Scholar
  133. Ma JG, Zheng WB, Zhou DH, Qin SY, Yin MY, Zhu XQ, Hu GX. First Report of Bovine Leukemia Virus Infection in Yaks (Bos mutus) in China. Biomed Res Int. 2016:9170167.Google Scholar
  134. Kobayashi S, Tsutsui T, Yamamoto T, Hayama Y, Kameyama K, Konishi M, Murakami K. Risk factors associated with within-herd transmission of bovine leukemia virus on dairy farms in Japan. BMC Vet Res. 2010;6:1.PubMedPubMed CentralView ArticleGoogle Scholar
  135. Murakami K, Kobayashi S, Konishi M, Kameyama K, Yamamoto T, Tsutsui T. The recent prevalence of bovine leukemia virus (BLV) infection among Japanese cattle. Vet Microbiol. 2011;148:84–8.PubMedView ArticleGoogle Scholar
  136. Murakami K, Kobayashi S, Konishi M, Kameyama K, Tsutsui T. Nationwide survey of bovine leukemia virus infection among dairy and beef breeding cattle in Japan from 2009-2011. J Vet Med Sci. 2013;75:1123–6.PubMedView ArticleGoogle Scholar
  137. Meas S, Ohashi K, Tum S, Chhin M, Te K, Miura K, Sugimoto C, Onuma M. Seroprevalence of bovine immunodeficiency virus and bovine leukemia virus in draught animals in Cambodia. J Vet Med Sci. 2000;62:779–81.PubMedView ArticleGoogle Scholar
  138. Nekoei S, Hafshejani TT, Doosti A, Khamesipour F. Molecular detection of bovine leukemia virus in peripheral blood of Iranian cattle, camel and sheep. Pol J Vet Sci. 2015;18:703–7.PubMedGoogle Scholar
  139. Mousavi S, Haghparast A, Mohammadi G, Tabatabaeizadeh SE. Prevalence of bovine leukemia virus (BLV) infection in the northeast of Iran. Vet Res Forum. 2014;5:135–9.PubMedPubMed CentralGoogle Scholar
  140. Trainin Z, Brenner J. The direct and indirect economic impacts of bovine leukemia virus infection on dairy cattle. Israel Journal of Veterinary Medicine. 2005;60:90–105.Google Scholar
  141. Hafez SM, Sharif M, Al-Sukayran A, Dela-Cruz D. Preliminary studies on enzootic bovine leukosis in Saudi dairy farms. Dtsch Tierarztl Wochenschr. 1990;97:61–3.PubMedGoogle Scholar
  142. Burgu I, Alkan F, Karaoglu T, Bilge-Dagalp S, Can-Sahna K, Gungor B, Demir B. Control and eradication programme of enzootic bovine leucosis (EBL) from selected dairy herds in Turkey. Dtsch Tierarztl Wochenschr. 2005;112:271–4.PubMedGoogle Scholar
  143. Zhao X, Buehring GC. Natural genetic variations in bovine leukemia virus envelope gene: possible effects of selection and escape. Virology. 2007;366:150–65.PubMedView ArticleGoogle Scholar
  144. Molteni E, Agresti A, Meneveri R, Marozzi A, Malcovati M, Bonizzi L, Poli G, Ginelli E. Molecular characterization of a variant of proviral bovine leukaemia virus (BLV). Zentralbl Veterinarmed B. 1996;43:201–11.PubMedView ArticleGoogle Scholar
  145. Derse D, Diniak AJ, Casey JW, Deininger PL. Nucleotide sequence and structure of integrated bovine leukemia virus long terminal repeats. Virology. 1985;141:162–6.PubMedView ArticleGoogle Scholar
  146. Yang Y, Kelly PJ, Bai J, Zhang R, Wang C. First molecular characterization of bovine leukemia virus infections in the Caribbean. PLoS One. 2016;11:e0168379.PubMedPubMed CentralView ArticleGoogle Scholar
  147. Dube S, Dolcini G, Abbott L, Mehta S, Dube D, Gutierrez S, Ceriani C, Esteban E, Ferrer J, Poiesz B. The complete genomic sequence of a BLV strain from a Holstein cow from Argentina. Virology. 2000;277:379–86.PubMedView ArticleGoogle Scholar
  148. Dube S, Abbott L, Dube DK, Dolcini G, Gutierrez S, Ceriani C, Juliarena M, Ferrer J, Perzova R, Poiesz BJ. The complete genomic sequence of an in vivo low replicating BLV strain. Virol J. 2009;6:120.PubMedPubMed CentralView ArticleGoogle Scholar
  149. Lim SI, Jeong W, Tark DS, Yang DK, Kweon CH. Agar gel immunodiffusion analysis using baculovirus-expressed recombinant bovine leukemia virus envelope glycoprotein (gp51/gp30(T-)). J Vet Sci. 2009;10:331–6.PubMedPubMed CentralView ArticleGoogle Scholar
  150. Inoue E, Matsumura K, Maekawa K, Nagatsuka K, Nobuta M, Hirata M, Minagawa A, Osawa Y, Okazaki K. Genetic heterogeneity among bovine leukemia viruses in Japan and their relationship to leukemogenicity. Arch Virol. 2011;156:1137–41.PubMedView ArticleGoogle Scholar
  151. Ababneh MM, Al-Rukibat RK, Hananeh WM, Nasar AT, Al-Zghoul MB. Detection and molecular characterization of bovine leukemia viruses from Jordan. Arch Virol. 2012;157:2343–8.PubMedView ArticleGoogle Scholar
  152. Rodriguez SM, Florins A, Gillet N, de Brogniez A, Sanchez-Alcaraz MT, Boxus M, Boulanger F, Gutierrez G, Trono K, Alvarez I, et al. Preventive and therapeutic strategies for bovine leukemia virus: lessons for HTLV. Viruses. 2011;3:1210–48.PubMedPubMed CentralView ArticleGoogle Scholar
  153. Inoue E, Matsumura K, Soma N, Hirasawa S, Wakimoto M, Arakaki Y, Yoshida T, Osawa Y, Okazaki K. L233P mutation of the tax protein strongly correlated with leukemogenicity of bovine leukemia virus. Vet Microbiol. 2013;167:364–71.PubMedView ArticleGoogle Scholar
  154. Murakami H, Asano S, Uchiyama J, Sato R, Sakaguchi M, Tsukamoto K. Bovine leukemia virus G4 enhances virus production. Virus Res. 2017;238:213–7.PubMedView ArticleGoogle Scholar

Copyright

© The Author(s). 2017

Advertisement