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Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review

Virology Journal volume 21, Article number: 59 (2024) Cite this article

Abstract

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.

Introduction

Acute respiratory tract infections (ARTIs) are responsible for the high morbidity and mortality of human beings, which have been considered one of the most significant factors threatening public health worldwide [1]. Moreover, ARTIs often result in lower respiratory tract infections (LRTIs) in clinical, which are responsible for millions of deaths worldwide [2]. Numerous viruses, such as the coronavirus, influenza virus, and human respiratory syncytial virus (hRSV), and others, are responsible for the incidence of ARTIs. In 2001, a research team in the Netherlands first discovered a novel virus associated with ARTIs, which was named human metapneumovirus (HMPV) [3]. Subsequently, the prevalence of HMPV has been documented in many countries and is considered a leading cause of ARTIs worldwide owing to the limited prevention and control measures [4, 5]. The clinical symptoms of HMPV infection in infants, elderly individuals, and immunocompromised individuals are mainly characterized by fever, cough, and gasp for breath, etc.,[6], which are similar to those of other common ARTIs-related viruses’ infection, including human bocavirus and hRSV [7].

HMPV is an enveloped, non-segmented, negative-stranded virus that belongs to the subfamily Pneumovirinae [8]. The HMPV genome (nearly 13 kb) contains eight genes that encode nine proteins, namely nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), matrix-2 proteins (M2-1 and M2-2), small hydrophobic (SH) protein, glycoprotein (G), and large (L) polymerase protein [9]. According to the genetic features of the F and G genes, HMPV strains prevalent worldwide could be classified into four genotypes (A1, A2, B1 and B2), and further divided into six lineages (A1, A2a, A2b, A2c, B1, and B2) [10, 11]. Notably, co-prevalence of several sub-genotypes or sub-lineages of HMPV has been frequently reported in the areas under investigation, while the thorough relationship between the disease severity and HMPV genotype is yet unclear [12, 13].

HMPV has been widely prevalent worldwide and continuously brings a significant medical burden to the local area, as effective vaccine or antiviral drug for treating or preventing HMPV infection is not licensed [14]. For instance, HMPV infection is associated with nearly one million outpatient clinic visits with clinical symptoms of ARTIs, and the disease caused by HMPV infection poses huge threats to the health of more than 86% of children aged below 5 years worldwide [15, 16]. Thus, a comprehensive understanding of the epidemiological characteristics, and detection approaches targeting HMPV would be beneficial for preventing this disease. This review provides updated information on HMPV in China, mainly focusing on its diagnosis approaches, prevalence, and genotype characteristics.

Current molecular diagnosis methods for HMPV detection

Early diagnosis of HMPV infection will help to develop effective measures against the disease, such as limiting the outbreak and providing timely care for the patients. Since the highly conserved F protein amino acid sequences of HMPV and RSV [17], limited serological technologies were developed for detecting HMPV-specific antibodies [18,19,20,21]. Thus a variety of molecular diagnosis methods, probing viral nucleic acids, have been invented for HMPV molecular detection, which mainly include the reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and reverse transcription loop-mediated isothermal amplification (RT-LAMP), etc., (as summarized in Table 1).

Table 1 Summary of HMPV molecular diagnostic approaches and their characteristics
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Molecular detection methods developed based on PCR

RT-PCR

In the past decades, RT-PCR assays have been widely applied for viral molecular detection, including HMPV. Generally, the genomic regions with high sequence homology of HMPV, such as the F and N genes, are employed as molecular markers for developing the RT-PCR methods, and these targeted regions can be used for genotype analysis [22, 23]. Li et al. developed a GenomeLab Gene Expression Profiler genetic analysis system (GeXP) based multiplex RT-PCR method for rapid and sensitive detection of sixteen ARTIs-related pathogens (including HMPV), and the detection limit of each virus was 1000 copies/reaction when all viral targets were added into the reaction [24].

Generally, RT-PCR assays for pathogen detection display lower sensitivity compared with RT-qPCR methods, which also need complex instruments [25]. Thus, RT-PCR methods have been less applied for HMPV-clinical detection in recent years.

RT-qPCR

RT-qPCR is a highly sensitive, accurate, and efficient technology, which has been widely used for detecting viral nucleic acids [25,26,27,28]. Usually, RT-qPCR methods provide higher sensitivity, and lower probability of contamination compared to the conventional RT-PCR methods, thus which is designed as the gold standard diagnostic approach [29]. A TaqMan-based RT-qPCR method developed by Lu et al. in 2008 showed a limited detection of 10 copies/μL, 19.62% (31/158) clinical samples were detected positive for HMPV using the established RT-qPCR method, while only 13.92% (22/158) of tested samples were confirmed positive using the conventional RT-PCR method [26]. Sugimoto et al. developed a duplex RT-qPCR assay for HMPV detection, which could identify and differentiate between HMPV A and B subgroups with high sensitivity (< 10 copies/reaction) [27].

Since multiple virus infections result in ARTIs, multiplex RT-qPCR assays have been developed for synchronously detecting HMPV and other ARTIs-related pathogens. You et al. established a reliable triple TaqMan-based RT-qPCR method for detecting HMPV, RSV, and the internal control gene (GAPDH), and the limit of detection of the established method was 100 copies/reaction of both HMPV and RSV [28]. Moreover, the multiplex one-tube nested RT-qPCR assay established by Feng et al. [30], could differentiate RSV, human rhinovirus (HRV), and HMPV, and the analytical sensitivity of the developed method was 5 copies/reaction for all three pathogens.

In recent years, digital microfluidic (DMF) technology has been applied in various fields including pathogen diagnosis [31]. Huang et al. developed an RT-qPCR platform combined with DMF technology for multiple detection of eleven respiratory pathogens including HMPV [32]. The sensitivities of the off-chip and on-chip RT-qPCR methods for multiple pathogens detection were ≤ 150 copies/reaction and ≤ 120 copies/reaction, respectively [32].

Nucleic acid isothermal amplification methods

LAMP

The LAMP technology, first invented by a Japanese team in 2000, is one of the most widely used isothermal methods in pathogen diagnosis [33]. Song et al. used the online LAMP primer design software Primer-Explorer V4 to design four pairs of primers targeting the M genes, to establish two RT-LAMP reactions for detecting and differentiating HMPV genotypes A and B, respectively [34]. The limit of detection (LOD) of the established method for HMPV genotypes A and B was 4.33 copies/μL and 3.53 copies/μL, respectively, which was 10 times more sensitive than the conventional RT-PCR methods [34]. Similarly, Wang et al. designed three pairs of primers targeting the N gene for HMPV detection. The established method showed a sensitivity level of < 10 copies/μL, which was more sensitive than the RT-PCR method [35].

Collectively, LAMP is performed in an isothermal environment (~ 65℃) with high amplification efficiency, which does not need complex equipment for thermal change. Meanwhile, the LAMP method displays higher specificity since two or three pair of primers are included in the reaction system, which can also improve the amplification efficiency [36]. Moreover, the detection results of the LAMP method can be observed and judged via the naked eyes, which further simplify the detection procedures [35, 36].

Recombinase-aided amplification (RAA)

RAA is a newly invented thermostatic amplification method, which can be performed with easy operation processes, simple equipment, and high amplification efficiency, and has been widely applied in field diagnosis of different pathogens [37]. Jiao et al. used the conservative region of the HMPV N gene to design primers for inventing the RT-RAA method, the LOD of the established method was 100 copies/μL, which was significantly lower than the commercial RT-qPCR method [38]. Moreover, the RT-RAA reaction system was set 39℃ for 15 min, which needed less running time compared with the RT-qPCR method [38].

CRISPR-Cas12a

Clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated proteins (Cas) have been widely applied in gene editing areas [39]. According to the genetic characteristics of the Cas gene in prokaryotes, the Cas protein families have been divided into three types [40]. Among these, the CRISPR-Cas12a system is considered a powerful tool for detecting nucleic acids in vitro [41]. In addition, the sensitivity and robustness of the CRISPR-Cas12a detection system could be greatly improved by combining with simultaneously reverse transcription and isothermal amplification technologies, such as LAMP [42], RAA [43], and recombinase polymerase amplification (RPA) [44]. Moreover, the CRISPR-Cas12a detection result can be observed via the naked eye when combined with lateral flow (LF), thus the established technology might be applied in these point-of-need places, such as airports and customs centers [45].

Qian et al. successfully established an HMPV RNA detection technique via combining RT-RPA with the CRISPR-Cas12a system. Briefly, the HMPV N gene was amplified via RT-RPA, the products were detected via CTISPR-Cas12a combined with LF [45]. Overall, the RT-RPA combined with Cas12a-based LF assay could be completed within 30 min, with an LOD of < 700 copies/mL [45]. Moreover, the established RT-RPA-Cas12a-LF method showed 96.4% detection coincidence with the quantitative RT-PCR assay, indicating that it would be an alternative tool for HMPV diagnosis without specialized equipment [45].

Metagenomic next-generation sequencing (mNGS)

mNGS is an emerging high-throughput diagnostic method that has been widely employed for virus genome sequencing, identification of novel pathogens, and other research [46]. When novel pathogens emerge, traditional detection methods (such as RT-PCR and RT-qPCR) might not be able to identify these new pathogens, while the mNGS can identify unknown or emerging pathogens [47]. Moreover, mNGS can be also used to amplify the whole viral genome with high accuracy, while the RNA genome must be reverse transcripted into cDNA before sequencing using Illumina and Sanger sequencing [37]. Xu et al. used the nanopore metagenomic sequencing technology to investigate the nosocomial transmission of HMPV among hematology patients, this method successfully generated HMPV reads of 80% (20/25) samples and obtained the complete HMPV genomes from 15 samples [48]. These data indicated that this technology can be used for diagnosing HMPV infection, while the sensitivity should be further improved [48].

Virus isolation

Virus isolation from the clinical samples is regarded as a gold standard for pathogen diagnosis, which is the initial step to developing vaccines and investigating viral pathogenesis [49]. Usually, the human Chang conjunctiva cell line (clone 1-5C4), LLC-MK2 cell line, and feline kidney CRFK cell line are suitable for HMPV isolation, and the LLC-MK2 cell line was more frequently used in HMPV isolation and cultivation [50, 51].

The procedures of virus isolation mainly include two steps: 1) the supernatants of the HMPV-positive sample are incubated with cell monolayer; 2) after 48–96 h of post-infection, the HMPV antigens or nucleic acids could be detected via serological or molecular detection methods. As HMPV grows slowly in cell lines, and cytopathic effects are rarely observed in HMPV-cell lines, subsequent serological/molecular assays are frequently used to detect HMPV antigens/nucleic acids [51].

Current epidemiology of HMPV in China

Since the first document of HMPV outbreaks in China in 2003 [52], the potential threats to public health have attracted widespread attention, thus epidemiological investigations have been frequently performed to monitor the prevalence of HMPV in China. To offer comprehensive and updated information on these, a total of 56 representative studies focusing on HMPV epidemiology across different regions in China were collected from the Chinese database and English database, the research was reported from January 1, 2003, to December 31, 2023 (Fig. 1). the detailed information of these research were shown in Supplementary Table 1.

Fig. 1
figure 1

Current epidemiology of HMPV in China. results of 56 representative studies investigating the epidemiological characteristics of HMPV in human populations across distinct regions covering 18 provinces or regions. These studies were collected from the English and Chinese databases from January 1, 2003, to December 31, 2023. Data of these provinces or regions marked with white were not available

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Risk factors associated with HMPV epidemiology in China

A total of 188,104 clinical samples and 8846 HMPV-positive cases are included in this review, which yields the average positive rate of 4.70% (95% CI 4.61–4.80). In detail, the prevalence of HMPV among patients with acute respiratory illness from different provinces/regions ranged from 0.97% (95% CI 0.74–1.20) to 15.88% (95% CI 14.41–17.35). The highest prevalence of HMPV was observed in Chongqing city (15.88%, 95% CI 14.41–17.35), Henan (7.05%, 95% CI 5.48–8.62), Tianjin (6.45%, 95% CI 3.72–9.18), and Jiangsu (6.26%, 95% CI 6.02–6.50), while Shanghai, Jiangxi, Hainan, and Beijing showed the lowest prevalence, with < 3.0%.

Next, the potential risk factors in subgroups associated with HMPV infection, including gender, age, season, case type, and others, were estimated in this study. As shown in Table 2, in the age subgroups, the detection rate of HMPV infection among patients aged > 60 months (1.47%, 95% CI 1.30–1.64) was significantly lower than other age subgroups, while the prevalence of HMPV infection among in other age subgroups (< 6 months, 6–12 months, 12–36 months, and 36–60 months) showed no significant difference. Among different seasons, the highest positive rate of HMPV infection among patients was detected in spring (12.13%), followed by winter (3.56%), while the prevalence of which in summer (1.28%) and autumn (1.32%) showed no significant difference.

Table 2 Pooled molecular prevalence of HMPV infection in China
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The epidemiological results of 17 studies showed that there is no significant relationship between gender and HMPV infection, the average positive rate of HMPV infection among male and female was 3.48% (95% CI 3.33–3.62) and 5.11% (95% CI 4.88–5.34). Moreover, the positive rate of HMPV-infected inpatients (3.56%, 95% CI 3.24–3.88) was not significantly different between the outpatients (3.22%, 95% CI 2.72–3.72).

The genetic features of HMPV in China

According to the genetic characteristics of HMPV, which could be divided into six lineages (A1, A2a, A2b, A2c, B1, and B2) [103, 104]. Though the relationships between pathogenicity and different HMPV lineages have been not fully explored, it is necessary to monitor the geographical distribution of different HMPV lineages in China. In this review, a total of 1253 HMPV gene sequences (G, F, M, or complete genome) were summarized in 19 articles to explore the genetic features of HMPV strains prevalent in China. As shown in Table 3, 8, 35, 544, 85, 299, and 282 HMPV strains belonged to the A1, A2, A2b, A2C, B1, and B2 lineages, which accounted for 0.64%, 2.79%, 43.42%, 6.78%, 23.86%, and 22.51%, respectively. The summarized results indicated that the A2b, B1, and B2 strains are the predominant lineages prevalent in China, while HMPV lineages prevalent in different provinces/regions in China are diverse. For example, the A2C was the predominant lineage prevalent in Henan province, while B1 and B2, but not A2b or A2C, predominated in Zhejiang province (Table 3).

Table 3 The lineage and its proportion of HMPV strains prevalent in different regions/provinces in China
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Conclusion and further directions

HMPV is still one of the major infectious viruses that cause ARTIs today, and it has been continuously posing huge economic burdens on the World Public Health Organization. Despite numerous efforts focused to develop diagnostic technologies for HMPV detection, epidemiological surveys, vaccines and other antiviral agents against this pathogen, there are currently no effective vaccines or medications against HMPV infection [15]. In light of this, rapid identification of positive cases and comprehensive investigation of HMPV epidemiological features are essential to prevent HMPV outbreaks and lessen their harmful effects.

There are currently many nucleic acid-based technologies for molecular HMPV detection available, which significantly lessen the challenge of HMPV diagnosis in various diagnostic contexts [22,23,24, 26,27,28, 34, 35, 38, 45, 48]. Among these, RT-PCR has been extensively used for pathogen detection, while this method is not appropriate for early HMPV diagnosis because of its low sensitivity [22,23,24]. The RT-qPCR method has a higher sensitivity than the traditional RT-PCR, and requires less operation time and fewer equipment, thus RT-qPCR has been widely used for the timely molecular detection of HMPV [26]. Additionally, a number of multiple RT-qPCR techniques have been developed and are used to simultaneously detect different pathogens including HMPV, in light of the relatively low prevalence of HMPV compared to other ARTIs-related viruses and the frequent occurrence of co-infection[27, 28]. Compared with the single RT-qPCR, multiple RT-qPCR methods are less costly and less time-consuming [27, 28].

Moreover, visual detection methods such as LAMP [34], RAA [38], and CRISPR/Cas12a combined with RPA [45], have also been developed for HMPV detection. These detection methods exhibit high sensitivity and do not require complex or expensive equipment, making them alternative approaches for HMPV detection in certain special occasions, such as field inspections at home or customs centers. Furthermore, mNGS is an emerging molecular detection technology that can directly identify a large number of pathogenic microorganisms in clinical samples, as well as amplify the complete genome of causative agents [105, 106]. While mNGS is time-consuming and more expensive compared to other molecular detection technologies, it may not be suitable for severely infected patients [48]. Thus, each molecular detection method has its own advantages and disadvantages. These characteristics should be fully considered in the clinical application.

In terms of the epidemiological characteristics of HMPV in China, the documents obtained from English and Chinese databases showed that HMPV has been widely prevalent in different regions of China. Although the prevalence of HMPV is relatively lower than some ARTIs-related viruses, such as HRV and RSV, the threats of it poses to public health cannot be ignored [107]. Overall, the pooled molecular prevalence of HMPV was 4.70% (95% CI 4.61–4.80), as supported by a nationwide prospective surveillance survey conducted in China, which showed a 4.1% HMPV-positive rate among 231,107 eligible patients with acute respiratory infection from 2009 to 2019 [107]. Notably, the prevalence of HMPV varied significantly by geographical region. This variation may be attributed to the differences in molecular detection methods, sampling sizes, patients ages, and other factors, all of which require further investigation.

The results of additional analysis revealed a significant association between the occurrence of HMPV infection and sampling season as well as patients age. In terms of sampling seasons, patients with ARTIs in spring had nearly 9 times the risk of HMPV infection compared to those in summer and autumn. As for age, the prevalence of HMPV among patients with ARTIs was significantly higher in young children (< 60 months) compared to older patients (> 60 months). Young children are at a high risk of HMPV infection in spring, while the threat of this pathogen to elderly people in other seasons should not be neglected. However, the gender and disease severity (inpatients or outpatients) had limited effects on the rates of HMPV infection among patients in China.

Due to the significant genetic variation of HMPV strains, they can be divided into multiple genotypes (A1, A2, B1, B2) and lineages (A1, A2a, A2b, A2c, B1, B2) [10, 11]. It is important to note that the genotypes or lineages of HMPV may vary from one region to another [5, 108]. Our summarized data show that at least five HMPV lineages (A1, A2b, A2C, B1, and B2) have been prevalent in China, while the lineages and proportions of HMPV vary greatly from province to province or region to region. Overall, the A2b, B1, and B2 lineages have become the predominant strains in China, while the A1 lineage was seldom detected in the regions under investigation. However, several characteristics of different HMPV lineages have not been comprehensively uncovered, including virulence, pathogenicity, and clinical symptoms. These issues need to be addressed in the future.

It is worth noting that the epidemiological characteristics of HMPV in China were not comprehensively analyzed in this review, and several factors contributed to this. Firstly, the research scope in this review may not cover all available reports. Secondly, although 56 representative studies were included in this review to assess the prevalence of HMPV in China, essential background information such as sampling season and year, disease severity level (inpatients or outpatients), viral load of the tested sample, and other risk factors were not provided in some of the papers. Thirdly, most of the HMPV epidemiological research has been reported in Guangdong, Jiangsu, and Beijing. The epidemiological characteristics of HMPV in other regions or provinces were relatively limited, and even in deficiency. Fourthly, this review summarized the types and proportions of different HMPV lineages in the investigated regions. However, most of the papers did not provide essential information on viral load, clinical signs, or disease severity of patients infected with different HMPV lineages. These limitations hinder a comprehensive evaluation of the epidemiological features of HMPV in China. Therefore, it is suggested that future HMPV epidemiological survey should overcome these potential drawbacks.

In summary, a variety of molecular diagnostic methods have been developed for detecting HMPV in China. RT-PCR, RT-qPCR, and multiple RT-qPCR are the most widely used approaches for clinical HMPV detection. As alternative options, other visual detection methods should be implemented in clinical testing as early as possible, with the consideration of lower cost, higher sensitivity, and higher convenience. The summarized data showed a relatively low prevalence (4.70%) of HMPV infection among patients with ARTIs in China. The prevalence was significantly associated with sampling seasons and patients' ages. Moreover, multiple HMPV lineages are prevalent in China, with high proportions of the A2b, B1, and B2 lineages. Given the persistent threat of HMPV to public health [109], it is crucial to continue monitoring the epidemiological spread and genetic evolution characteristics of this pathogen in China.

Data availability statement

The data presented in this review can be found in online repositories.

Abbreviations

ARTIs:

Acute respiratory tract infections

LRTIs:

Lower respiratory tract infections

HRSV:

Human respiratory syncytial virus

HMPV:

Human metapneumovirus

RT-PCR:

Reverse transcription polymerase chain reaction

RT-qPCR:

Real-time quantitative reverse transcription polymerase chain reaction

RT-LAMP:

Reverse transcription loop-mediated isothermal amplification

GeXP:

GenomeLab Gene Expression Profiler genetic analysis system

HRV:

Human rhinovirus

DMF:

Digital microfluidic

LOD:

Limit of detection

RAA:

Recombinase-aided amplification

CRISPR:

Clustered regularly interspaced short palindromic repeat

Cas:

CRISPR-associated proteins

RPA:

Recombinase polymerase amplification

LF:

Lateral flow

mNGS:

Metagenomic next-generation sequencing

References

  1. Jefferson T, Dooley L, Ferroni E, Al-Ansary LA, van Driel ML, Bawazeer GA, et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst Rev. 2023;1(1):CD006207. https://doi.org/10.1002/14651858.CD006207.

    Article  PubMed  Google Scholar 

  2. Schwartz JL. The Spanish Flu, epidemics, and the turn to biomedical responses. Am J Public Health. 2018;108(11):1455–8. https://doi.org/10.2105/AJPH.2018.304581.

    Article  PubMed Central  PubMed  Google Scholar 

  3. van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RA, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7(6):719–24. https://doi.org/10.1038/89098.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Du Y, Li W, Guo Y, Li L, Chen Q, He L, Shang S. Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China. J Med Virol. 2022;94(11):5401–8. https://doi.org/10.1002/jmv.28024.

    Article  CAS  PubMed  Google Scholar 

  5. Divarathna MVM, Rafeek RAM, Noordeen F. A review on epidemiology and impact of human metapneumovirus infections in children using TIAB search strategy on PubMed and PubMed Central articles. Rev Med Virol. 2020;30(1): e2090. https://doi.org/10.1002/rmv.2090.

    Article  PubMed  Google Scholar 

  6. Ogonczyk Makowska D, Hamelin MÈ, Boivin G. Engineering of live chimeric vaccines against human metapneumovirus. Pathogens. 2020;9(2):135. https://doi.org/10.3390/pathogens9020135.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Tang X, Dai G, Wang T, Sun H, Jiang W, Chen Z, et al. Comparison of the clinical features of human bocavirus and metapneumovirus lower respiratory tract infections in hospitalized children in Suzhou. China Front Pediatr. 2023;10:1074484. https://doi.org/10.3389/fped.2022.1074484.

    Article  PubMed  Google Scholar 

  8. Amarasinghe GK, Aréchiga Ceballos NG, Banyard AC, Basler CF, Bavari S, Bennett AJ, et al. Taxonomy of the order Mononegavirales: update 2018. Arch Virol. 2018;163(8):2283–94. https://doi.org/10.1007/s00705-018-3814-x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Ye H, Zhang S, Zhang K, Li Y, Chen D, Tan Y, et al. Epidemiology, genetic characteristics, and association with meteorological factors of human metapneumovirus infection in children in southern China: a 10-year retrospective study. Int J Infect Dis. 2023;137:40–7. https://doi.org/10.1016/j.ijid.2023.10.002.

    Article  CAS  PubMed  Google Scholar 

  10. Yi L, Zou L, Peng J, Yu J, Song Y, Liang L, et al. Epidemiology, evolution and transmission of human metapneumovirus in Guangzhou China, 2013–2017. Sci Rep. 2019;9(1):14022. https://doi.org/10.1038/s41598-019-50340-8.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  11. Tulloch RL, Kok J, Carter I, Dwyer DE, Eden JS. An amplicon-based approach for the whole-genome sequencing of human metapneumovirus. Viruses. 2021;13(3):499. https://doi.org/10.3390/v13030499.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Roussy JF, Carbonneau J, Ouakki M, Papenburg J, Hamelin MÈ, De Serres G, et al. Human metapneumovirus viral load is an important risk factor for disease severity in young children. J Clin Virol. 2014;60(2):133–40. https://doi.org/10.1016/j.jcv.2014.03.001.

    Article  PubMed  Google Scholar 

  13. Otomaru H, Nguyen HAT, Vo HM, Toizumi M, Le MN, Mizuta K, et al. A decade of human metapneumovirus in hospitalized children with acute respiratory infection: molecular epidemiology in central Vietnam, 2007–2017. Sci Rep. 2023;13(1):15757.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  14. Ma S, Zhu F, Xu Y, Wen H, Rao M, Zhang P, et al. Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus. Hum Vaccin Immunother. 2023;19(3):2293300. https://doi.org/10.1080/21645515.2023.2293300.

    Article  CAS  PubMed  Google Scholar 

  15. Van Den Bergh A, Bailly B, Guillon P, von Itzstein M, Dirr L. Antiviral strategies against human metapneumovirus: Targeting the fusion protein. Antiviral Res. 2022;207: 105405. https://doi.org/10.1016/j.antiviral.

    Article  PubMed  Google Scholar 

  16. Gálvez NMS, Andrade CA, Pacheco GA, Soto JA, Stranger V, Rivera T, et al. Host components that modulate the disease caused by hMPV. Viruses. 2021;13(3):519. https://doi.org/10.3390/v13030519.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Kim JI, Park S, Lee I, Park KS, Kwak EJ, Moon KM, et al. Genome-wide analysis of human metapneumovirus evolution. PLoS ONE. 2016;11(4): e0152962. https://doi.org/10.1371/journal.pone.0152962.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Percivalle E, Sarasini A, Visai L, Revello MG, Gerna G. Rapid detection of human metapneumovirus strains in nasopharyngeal aspirates and shell vial cultures by monoclonal antibodies. J Clin Microbiol. 2005;43(7):3443–6. https://doi.org/10.1128/JCM.43.7.3443-3446.2005.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Okamoto M, Sugawara K, Takashita E, Muraki Y, Hongo S, Mizuta K, et al. Development and evaluation of a whole virus-based enzyme-linked immunosorbent assay for the detection of human metapneumovirus antibodies in human sera. J Virol Methods. 2010;164(1–2):24–9. https://doi.org/10.1016/j.jviromet.2009.11.019.

    Article  CAS  PubMed  Google Scholar 

  20. Liu L, Bastien N, Sidaway F, Chan E, Li Y. Seroprevalence of human metapneumovirus (hMPV) in the Canadian province of Saskatchewan analyzed by a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay. J Med Virol. 2007;79(3):308–13. https://doi.org/10.1002/jmv.20799.

    Article  CAS  PubMed  Google Scholar 

  21. Ishiguro N, Akutsu Y, Azuma K, Yonekawa M, Sato D, Ishizaka A, et al. Evaluation of a novel immunochromatographic assay using monoclonal antibodies against the matrix protein of human metapneumovirus. Clin Lab. 2021;67(10):1. https://doi.org/10.7754/Clin.Lab.2021.210232.

    Article  Google Scholar 

  22. Cong S, Wang C, Wei T, Xie Z, Huang Y, Tan J, et al. Human metapneumovirus in hospitalized children with acute respiratory tract infections in Beijing, China. Infect Genet Evol. 2022;106: 105386. https://doi.org/10.1016/j.meegid.2022.105386.

    Article  CAS  PubMed  Google Scholar 

  23. Wang C, Wei T, Ma F, Wang H, Guo J, Chen A, et al. Epidemiology and genotypic diversity of human metapneumovirus in paediatric patients with acute respiratory infection in Beijing, China. Virol J. 2021;18(1):40. https://doi.org/10.1186/s12985-021-01508-0.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Li J, Mao NY, Zhang C, Yang MJ, Wang M, Xu WB, et al. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes. BMC Infect Dis. 2012;12:189. https://doi.org/10.1186/1471-2334-12-189.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Guo X, Cui YX, Zhuge SR, Liu XM. Comparative study on real-time PCR and RT-PCR testing methods for detecting human metapneumovirus. Guiyang Med Coll J. 2015;40:834–8 ((in Chinese)).

    Google Scholar 

  26. Lu JR, Zhang LL, Tan WJ, Zhou WM, Wang Z, Peng K, et al. Development and application of real-time RT-PCR assay for detection of human metapneumovirus in Beijing. Lett Biotechnol. 2008;19:207–9 ((in Chinese)).

    CAS  Google Scholar 

  27. Sugimoto S, Kawase M, Suwa R, Kakizaki M, Kume Y, Chishiki M, et al. Development of a duplex real-time RT-PCR assay for the detection and identification of two subgroups of human metapneumovirus in a single tube. J Virol Methods. 2023;322: 114812. https://doi.org/10.1016/j.jviromet.2023.114812.

    Article  CAS  PubMed  Google Scholar 

  28. You HL, Chang SJ, Yu HR, Li CC, Chen CH, Liao WT. Simultaneous detection of respiratory syncytial virus and human metapneumovirus by one-step multiplex real-time RT-PCR in patients with respiratory symptoms. BMC Pediatr. 2017;17(1):89. https://doi.org/10.1186/s12887-017-0843-7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Garbuglia AR, Lapa D, Pauciullo S, Raoul H, Pannetier D. Nipah virus: an overview of the current status of diagnostics and their role in preparedness in endemic countries. Viruses. 2023;15(10):2062. https://doi.org/10.3390/v15102062.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Feng ZS, Zhao L, Wang J, Qiu FZ, Zhao MC, Wang L, et al. A multiplex one-tube nested real time RT-PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus. Virol J. 2018;15(1):167. https://doi.org/10.1186/s12985-018-1061-0.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Xu X, Cai L, Liang S, Zhang Q, Lin S, Li M, Y, et al. Digital microfluidics for biological analysis and applications. Lab Chip. 2023;23(5):1169–91. https://doi.org/10.1039/d2lc00756h.

    Article  CAS  PubMed  Google Scholar 

  32. Huang H, Huang K, Sun Y, Luo D, Wang M, Chen T, et al. A digital microfluidic RT-qPCR platform for multiple detections of respiratory pathogens. Micromachines (Basel). 2022;13(10):1650. https://doi.org/10.3390/mi13101650.

    Article  PubMed  Google Scholar 

  33. Flores-Contreras EA, Carrasco-González JA, Linhares DCL, Corzo CA, Campos-Villalobos JI, Henao-Díaz A, et al. Emergent molecular techniques applied to the detection of porcine viruses. Vet Sci. 2023;10(10):609. https://doi.org/10.3390/vetsci10100609.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Song Q, Zhu R, Sun Y, Zhao L, Wang F, Deng J, et al. Identification of human metapneumovirus genotypes A and B from clinical specimens by reverse transcription loop-mediated isothermal amplification. J Virol Methods. 2014;196:133–8. https://doi.org/10.1016/j.jviromet.2013.10.037.

    Article  CAS  PubMed  Google Scholar 

  35. Wang X, Zhang Q, Zhang F, Ma F, Zheng W, Zhao Z, et al. Visual detection of the human metapneumovirus using reverse transcription loop-mediated isothermal amplification with hydroxynaphthol blue dye. Virol J. 2012;9:138. https://doi.org/10.1186/1743-422X-9-138.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Wang D, Wang Y, Zhu K, Shi L, Zhang M, Yu J, et al. Detection of cassava component in sweet potato noodles by real-time loop-mediated isothermal amplification (real-time LAMP) method. Molecules. 2019;24(11):2043. https://doi.org/10.3390/molecules24112043.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Pan J, Zeng M, Zhao M, Huang L. Research progress on the detection methods of porcine reproductive and respiratory syndrome virus. Front Microbiol. 2023;14:1097905. https://doi.org/10.3389/fmicb.2023.1097905.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Jiao SL, Xie L, Mao Y, NI HX, Li YD,. Establishment of a reverse transcriptase-mediated isothermal amplication fluorescence assay for detection of Human metapneumovirus. Chin J Zoonos. 2023;39:780–3 ((in Chinese)).

    Google Scholar 

  39. Li X, Zhong J, Li H, Qiao Y, Mao X, Fan H, et al. Advances in the application of CRISPR-Cas technology in rapid detection of pathogen nucleic acid. Front Mol Biosci. 2023;10:1260883. https://doi.org/10.3389/fmolb.2023.1260883.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Makarova KS, Aravind L, Wolf YI, Koonin EV. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol Direct. 2011;6:38. https://doi.org/10.1186/1745-6150-6-38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Yang R, Zhao L, Wang X, Kong W, Luan Y. Recent progress in aptamer and CRISPR-Cas12a based systems for non-nucleic target detection. Crit Rev Anal Chem. 2023;1:1–18. https://doi.org/10.1080/10408347.2023.2197062.

    Article  CAS  Google Scholar 

  42. Lei L, Liao F, Tan L, Duan D, Zhan Y, Wang N, et al. LAMP coupled CRISPR-Cas12a module for rapid, sensitive and visual detection of porcine circovirus 2. Animals (Basel). 2022;12(18):2413. https://doi.org/10.3390/ani12182413.

    Article  PubMed  Google Scholar 

  43. Zhao Z, Wang S, Dong Z, Fan Q, Lei R, Kuang R, et al. One-step reverse-transcription recombinase-aided amplification CRISPR/Cas12a-based lateral flow assay for fast field screening and accurate differentiation of four major tobamoviruses infecting tomato and pepper. J Agric Food Chem. 2023. https://doi.org/10.1021/acs.jafc.3c05268.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Li Y, Wang X, Xu R, Wang T, Zhang D, Qian W. Establishment of RT-RPA-Cas12a assay for rapid and sensitive detection of human rhinovirus B. BMC Microbiol. 2023;23(1):333. https://doi.org/10.1186/s12866-023-03096-1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Qian W, Huang J, Wang T, He X, Xu G, Li Y. Visual detection of human metapneumovirus using CRISPR-Cas12a diagnostics. Virus Res. 2021;305: 198568. https://doi.org/10.1016/j.virusres.2021.198568.

    Article  CAS  PubMed  Google Scholar 

  46. Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol. 2019;14:319–38. https://doi.org/10.1146/annurev-pathmechdis-012418-012751.

    Article  CAS  PubMed  Google Scholar 

  47. Zhao J, Ragupathy V, Liu J, Wang X, Vemula SV, El Mubarak HS, et al. Nanomicroarray and multiplex next-generation sequencing for simultaneous identification and characterization of influenza viruses. Emerg Infect Dis. 2015;21(3):400–8. https://doi.org/10.3201/eid2103.141169.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Xu Y, Lewandowski K, Jeffery K, Downs LO, Foster D, Sanderson ND, et al. Nanopore metagenomic sequencing to investigate nosocomial transmission of human metapneumovirus from a unique genetic group among haematology patients in the United Kingdom. J Infect. 2020;80(5):571–7. https://doi.org/10.1016/j.jinf.2020.02.003.

    Article  CAS  PubMed  Google Scholar 

  49. Tan L, Yao J, Yang Y, Luo W, Yuan X, Yang L, et al. Current status and challenge of pseudorabies virus infection in China. Virol Sin. 2021;36(4):588–607. https://doi.org/10.1007/s12250-020-00340-0.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Tollefson SJ, Cox RG, Williams JV. Studies of culture conditions and environmental stability of human metapneumovirus. Virus Res. 2010;151(1):54–9. https://doi.org/10.1016/j.virusres.2010.03.018.

    Article  CAS  PubMed  Google Scholar 

  51. Jeong S, Park MJ, Song W, Kim HS. Advances in laboratory assays for detecting human metapneumovirus. Ann Transl Med. 2020;8(9):608. https://doi.org/10.21037/atm.2019.12.42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Chan PK, Tam JS, Lam CW, Chan E, Wu A, Li CK, et al. Human metapneumovirus detection in patients with severe acute respiratory syndrome. Emerg Infect Dis. 2003;9(9):1058–63. https://doi.org/10.3201/eid0909.030304.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Zhu Y, Xu B, Li C, Chen Z, Cao L, Fu Z, et al. A Multicenter study of viral aetiology of community-acquired pneumonia in hospitalized children in Chinese mainland. Virol Sin. 2021;36(6):1543–53. https://doi.org/10.1007/s12250-021-00437-0.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Zhao H, Feng Q, Feng Z, Zhu Y, Ai J, Xu B, et al. Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study. Virol Sin. 2022;37(6):874–82. https://doi.org/10.1016/j.virs.2022.08.007.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Tang X, Dai G, Jiang X, Wang T, Sun H, Chen Z, et al. Clinical characteristics of pediatric respiratory tract infection and respiratory pathogen isolation during the coronavirus disease 2019 pandemic. Front Pediatr. 2022;9: 759213. https://doi.org/10.3389/fped.2021.759213.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Li L, Wang H, Liu A, Wang R, Zhi T, Zheng Y, et al. Comparison of 11 respiratory pathogens among hospitalized children before and during the COVID-19 epidemic in Shenzhen, China. Virol J. 2021;18(1):202. https://doi.org/10.1186/s12985-021-01669-y.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Xie Z, Xu J, Ren Y, Cui A, Wang H, Song J, et al. Emerging human metapneumovirus gene duplication variants in patients with severe acute respiratory infection, China, 2017–2019. Emerg Infect Dis. 2021;27(1):275–7. https://doi.org/10.3201/eid2701.201043.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Zhu R, Guo C, Zhao L, Deng J, Wang F, Sun Y, et al. Epidemiological and genetic characteristics of human metapneumovirus in pediatric patients across six consecutive seasons in Beijing, China. Int J Infect Dis. 2020;91:137–42. https://doi.org/10.1016/j.ijid.2019.11.012.

    Article  PubMed  Google Scholar 

  59. Li F, Zhang Y, Shi P, Cao L, Su L, Zhang Y, et al. Epidemiology of viruses causing pediatric community acquired pneumonia in Shanghai during 2010–2020: What happened before and after the COVID-19 outbreak? Infect Dis Ther. 2022;11(1):165–74. https://doi.org/10.1007/s40121-021-00548-x.

    Article  CAS  PubMed  Google Scholar 

  60. Li J, Song CL, Wang T, Ye YL, Du JR, Li SH, et al. Etiological and epidemiological characteristics of severe acute respiratory infection caused by multiple viruses and Mycoplasma pneumoniae in adult patients in Jinshan, Shanghai: a pilot hospital-based surveillance study. PLoS ONE. 2021;16(3): e0248750. https://doi.org/10.1371/journal.pone.0248750.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Cui A, Xie Z, Xu J, Hu K, Zhu R, Li Z, et al. Comparative analysis of the clinical and epidemiological characteristics of human influenza virus versus human respiratory syncytial virus versus human metapneumovirus infection in nine provinces of China during 2009–2021. J Med Virol. 2022;94(12):5894–903. https://doi.org/10.1002/jmv.28073.

    Article  CAS  PubMed  Google Scholar 

  62. Du Y, Li W, Guo Y, Li L, Chen Q, He L, et al. Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China. J Med Virol. 2022;94(11):5401–8. https://doi.org/10.1002/jmv.28024.

    Article  CAS  PubMed  Google Scholar 

  63. Mai W, Ren Y, Tian X, Al-Mahdi AY, Peng R, An J, et al. Comparison of common human respiratory pathogens among hospitalized children aged ≤ 6 years in Hainan Island, China, during spring and early summer in 2019–2021. J Med Virol. 2023;95(4): e28692. https://doi.org/10.1002/jmv.28692.

    Article  CAS  PubMed  Google Scholar 

  64. Ji L, Chen L, Xu D, Wu X. Molecular typing and epidemiological profiles of human metapneumovirus infection among children with severe acute respiratory infection in Huzhou. China Mol Biol Rep. 2021;48(12):7697–702. https://doi.org/10.1007/s11033-021-06776-1.

    Article  CAS  PubMed  Google Scholar 

  65. Shi T, Huang L. Prevalence of respiratory pathogens and risk of developing pneumonia under non-pharmaceutical interventions in Suzhou. China Epidemiol Infect. 2023;151: e82. https://doi.org/10.1017/S0950268823000626.

    Article  PubMed  Google Scholar 

  66. Zhang J, Yang T, Zou M, Wang L, Sai L. The epidemiological features of respiratory tract infection using the multiplex panels detection during COVID-19 pandemic in Shandong province, China. Sci Rep. 2023;13(1):6319. https://doi.org/10.1038/s41598-023-33627-9.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  67. Chan WS, Yau SK, To MY, Leung SM, Wong KP, Lai KC, et al. The seasonality of respiratory viruses in a Hong Kong hospital, 2014–2023. Viruses. 2023;15(9):1820. https://doi.org/10.3390/v15091820.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Liu WK, Chen DH, Tan WP, Qiu SY, Xu D, Zhang L, et al. Paramyxoviruses respiratory syncytial virus, parainfluenza virus, and human metapneumovirus infection in pediatric hospitalized patients and climate correlation in a subtropical region of southern China: a 7-year survey. Eur J Clin Microbiol Infect Dis. 2019;38(12):2355–64. https://doi.org/10.1007/s10096-019-03693-x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Zhao Y, Lu R, Shen J, Xie Z, Liu G, Tan W. Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China. BMC Infect Dis. 2019;19(1):729. https://doi.org/10.1186/s12879-019-4385-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Li YT, Liang Y, Ling YS, Duan MQ, Pan L, Chen ZG. The spectrum of viral pathogens in children with severe acute lower respiratory tract infection: A 3-year prospective study in the pediatric intensive care unit. J Med Virol. 2019;91(9):1633–42. https://doi.org/10.1002/jmv.25502.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Zhong P, Zhang H, Chen X, Lv F. Clinical characteristics of the lower respiratory tract infection caused by a single infection or coinfection of the human parainfluenza virus in children. J Med Virol. 2019;91(9):1625–32. https://doi.org/10.1002/jmv.25499.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Li X, Li J, Meng L, Zhu W, Liu X, Yang M, et al. Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu province, northwest China, 2011–2015. J Med Virol. 2018;90(5):828–35. https://doi.org/10.1002/jmv.25040.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Zhou JY, Peng Y, Peng XY, Gao HC, Sun YP, Xie LY, et al. Human bocavirus and human metapneumovirus in hospitalized children with lower respiratory tract illness in Changsha, China. Influenza Other Respir Viruses. 2018;12(2):279–86. https://doi.org/10.1111/irv.12535.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Ye C, Zhu W, Yu J, Li Z, Fu Y, Lan Y, et al. Viral pathogens among elderly people with acute respiratory infections in Shanghai, China: preliminary results from a laboratory-based surveillance, 2012–2015. J Med Virol. 2017;89(10):1700–6. https://doi.org/10.1002/jmv.24751.

    Article  PubMed Central  PubMed  Google Scholar 

  75. Yan XL, Li YN, Tang YJ, Xie ZP, Gao HC, Yang XM, et al. Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection. J Med Virol. 2017;89(4):589–97. https://doi.org/10.1002/jmv.24687.

    Article  CAS  PubMed  Google Scholar 

  76. Kong W, Wang Y, Zhu H, Lin X, Yu B, Hu Q, et al. Circulation of human metapneumovirus among children with influenza-like illness in Wuhan, China. J Med Virol. 2016;88(5):774–81. https://doi.org/10.1002/jmv.24411.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Wang D, Chen L, Ding Y, Zhang J, Hua J, Geng Q, et al. Viral etiology of medically attended influenza-like illnesses in children less than five years old in Suzhou, China, 2011–2014. J Med Virol. 2016;88(8):1334–40. https://doi.org/10.1002/jmv.24480.

    Article  PubMed Central  PubMed  Google Scholar 

  78. Zeng SZ, Xiao NG, Zhong LL, Yu T, Zhang B, Duan ZJ. Clinical features of human metapneumovirus genotypes in children with acute lower respiratory tract infection in Changsha, China. J Med Virol. 2015;87(11):1839–45. https://doi.org/10.1002/jmv.24249.

    Article  PubMed Central  PubMed  Google Scholar 

  79. Luo KM, Liang YW, Zhang SS. Detection and analysis of pandemic virus in children with acute respiratory tract infection in Yangshan from 2012 to 2014. Chin J Health Lab Tec. 2016;26:3004–6 ((in Chinese)).

    Google Scholar 

  80. Tian Y, Wei F, Zhang XJ, Liu BJ, Yu HL, Wang Y. Research on virus spectrum of 262 fever clinic patients with acute respiratory tract infection in Guiyang. Mod Prev Med. 2021;48:4382–6 ((in Chinese)).

    Google Scholar 

  81. Liu SW, Li JX, Gong T, Zhang YL, Shi Y, Xiao F, et al. Analysis of Human metapneumovirus infection in 2438 children with acute respiratory tract infection in Jiangxi province. Experim Lab Med. 2019;37:562–5 ((in Chinese)).

    CAS  Google Scholar 

  82. Liu AL, Liu SY, Liu J, Zhu CY, Guo LH. Gene analysis of pulmonary virus in the hospitalized children with acute upper respiratory trace infection and its present situation. J Clin Transfus Lab Med. 2018;20(2):150–3 ((in Chinese)).

    MathSciNet  Google Scholar 

  83. Peng F, Yang Y, Yu YF, Jiang XX. Infection status and genetic characteristics of human metapneumovirus in children with respiratory tract infection in Yueyang city. Pract Prev Med. 2023;30:936–9 ((in Chinese)).

    Google Scholar 

  84. Wei R, Yuan X, Tian XW, Lu YJ. Clinical and laboratory characteristics of human metapneumovirus infection children in a class 3 hospital in Wuhan. Lab Med. 2023;38:18–22 ((in Chinese)).

    Google Scholar 

  85. Peiris JS, Tang WH, Chan KH, Khong PL, Guan Y, Lau YL, et al. Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis. 2003;9(6):628–33. https://doi.org/10.3201/eid0906.030009.

    Article  PubMed Central  PubMed  Google Scholar 

  86. Lee N, Chan PK, Yu IT, Tsoi KK, Lui G, Sung JJ, et al. Co-circulation of human metapneumovirus and SARS-associated coronavirus during a major nosocomial SARS outbreak in Hong Kong. J Clin Virol. 2007;40(4):333–7. https://doi.org/10.1016/j.jcv.2007.08.015.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Mao HW, Yang XQ, Zhao XD. Characterization of human metapneumoviruses isolated in Chongqing. China Chin Med J (Engl). 2008;121(22):2254–7.

    Article  PubMed  Google Scholar 

  88. Liu WP, Zhang B, Xie ZP, Zhong LL, Qu XW, Zheng LS, et al. Analysis of human metapneumovirus genotype in Hunan, China and its attachment protein G sequence character. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008;22(2):101–3 ((in Chinese)).

    CAS  PubMed  Google Scholar 

  89. Li XY, Chen JY, Kong M, Su X, Yi YP, Zou M, et al. Prevalence of human metapneumovirus in hospitalized children with respiratory tract infections in Tianjin. China Arch Virol. 2009;154(11):1831–6. https://doi.org/10.1007/s00705-009-0492-8.

    Article  CAS  PubMed  Google Scholar 

  90. Ji W, Wang Y, Chen Z, Shao X, Ji Z, Xu J. Human metapneumovirus in children with acute respiratory tract infections in Suzhou, China 2005–2006. Scand J Infect Dis. 2009;41(10):735–44. https://doi.org/10.1080/00365540903148264.

    Article  PubMed  Google Scholar 

  91. Zou LR, Mo YL, Wu D, Fang L, Li H, Chen QX, et al. Investigation of human metapneumovirus in children with acute respiratory tract infections in Guangzhou areas. Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43(4):314–8 ((in Chinese)).

    CAS  PubMed  Google Scholar 

  92. Ren L, Gonzalez R, Wang Z, Xiang Z, Wang Y, Zhou H, et al. Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007. Clin Microbiol Infect. 2009;15(12):1146–53. https://doi.org/10.1111/j.1469-0691.2009.02746.x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Chen X, Zhang ZY, Zhao Y, Liu EM, Zhao XD. Acute lower respiratory tract infections by human metapneumovirus in children in Southwest China: a 2-year study. Pediatr Pulmonol. 2010;45(8):824–31. https://doi.org/10.1002/ppul.21264.

    Article  PubMed Central  PubMed  Google Scholar 

  94. Xiao NG, Xie ZP, Zhang B, Yuan XH, Song JR, Gao HC, et al. Prevalence and clinical and molecular characterization of human metapneumovirus in children with acute respiratory infection in China. Pediatr Infect Dis J. 2010;29(2):131–4. https://doi.org/10.1097/inf.0b013e3181b56009.

    Article  PubMed  Google Scholar 

  95. Li J, Wang Z, Gonzalez R, Xiao Y, Zhou H, Zhang J, et al. Prevalence of human metapneumovirus in adults with acute respiratory tract infection in Beijing. China J Infect. 2012;64(1):96–103. https://doi.org/10.1016/j.jinf.2011.10.011.

    Article  PubMed  Google Scholar 

  96. Jin Y, Zhang RF, Xie ZP, Yan KL, Gao HC, Song JR, et al. Newly identified respiratory viruses associated with acute lower respiratory tract infections in children in Lanzou, China, from 2006 to 2009. Clin Microbiol Infect. 2012;18(1):74–80. https://doi.org/10.1111/j.1469-0691.2011.03541.x.

    Article  CAS  PubMed  Google Scholar 

  97. Lu G, Li J, Xie Z, Liu C, Guo L, Vernet G, et al. Human metapneumovirus associated with community-acquired pneumonia in children in Beijing, China. J Med Virol. 2013;85(1):138–43. https://doi.org/10.1002/jmv.23438.

    Article  PubMed  Google Scholar 

  98. Wang Y, Chen Z, Yan YD, Guo H, Chu C, Liu J, et al. Seasonal distribution and epidemiological characteristics of human metapneumovirus infections in pediatric inpatients in Southeast China. Arch Virol. 2013;158(2):417–24. https://doi.org/10.1007/s00705-012-1492-7.

    Article  CAS  PubMed  Google Scholar 

  99. Zhang C, Du LN, Zhang ZY, Qin X, Yang X, Liu P, et al. Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Southwest China. J Clin Microbiol. 2012;50(8):2714–9.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Lu Y, Wang S, Zhang L, Xu C, Bian C, Wang Z, et al. Epidemiology of human respiratory viruses in children with acute respiratory tract infections in Jinan, China. Clin Dev Immunol. 2013;2013: 210490. https://doi.org/10.1155/2013/210490.

    Article  PubMed Central  PubMed  Google Scholar 

  101. Feng L, Li Z, Zhao S, Nair H, Lai S, Xu W, et al. Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009–2013. PLoS ONE. 2014;9(6): e99419. https://doi.org/10.1371/journal.pone.0099419.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  102. Wei T, Wang C, Ma F, Guo J, Chen A, Huang Y, et al. Whole genome sequencing and evolution analyses of Human metapneumovirus. Virus Genes. 2023;59(4):524–31. https://doi.org/10.1007/s11262-023-02001-2.

    Article  CAS  PubMed  Google Scholar 

  103. Nao N, Saikusa M, Sato K, Sekizuka T, Usuku S, Tanaka N, et al. Recent molecular evolution of human metapneumovirus (HMPV): subdivision of HMPV A2b strains. Microorganisms. 2020;8(9):1280. https://doi.org/10.3390/microorganisms8091280.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  104. Parida P, N S, E R S, Jagadesh A, Marate S, Govindakaranavar A. The emergence of human metapneumovirus G gene duplication in hospitalized patients with respiratory tract infection, India, 2016–2018. Mol Biol Rep. 2023; 50(2): 1109–1116. https://doi.org/10.1007/s11033-022-08092-8.

  105. Li Y, Lei J, Ren Z, Ma X. Case Report: Metagenomic next-generation sequencing assists in dynamic pathogen monitoring: powerful tool for progressing severe pneumonia. Front Cell Infect Microbiol. 2023;13:1230813. https://doi.org/10.3389/fcimb.2023.1230813.

    Article  PubMed Central  PubMed  Google Scholar 

  106. Suminda GGD, Bhandari S, Won Y, Goutam U, Kanth Pulicherla K, Son YO, et al. High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance. Comput Struct Biotechnol J. 2022;20:5378–92. https://doi.org/10.1016/j.csbj.2022.09.028.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Li ZJ, Zhang HY, Ren LL, Lu QB, Ren X, Zhang CH, et al. Etiological and epidemiological features of acute respiratory infections in China. Nat Commun. 2021;12(1):5026. https://doi.org/10.1038/s41467-021-25120-6.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  108. Kahn JS. Epidemiology of human metapneumovirus. Clin Microbiol Rev. 2006;19(3):546–57. https://doi.org/10.1128/CMR.00014-06.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Guo L, Li L, Liu L, Zhang T, Sun M. Neutralising antibodies against human metapneumovirus. Lancet Microbe. 2023;4(9):e732–44. https://doi.org/10.1016/S2666-5247(23)00134-9.

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the Xiangtan Medical Associated Project (No. 2022-xtyx-2), and the Project of Hunan Provincial Health Commission (No. D20230619358).

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Authors and Affiliations

  1. Xiangtan Central Hospital, Xiangtan, 411100, Hunan, China

    Yuan Feng, Bo Zhang, Haibin Yuan & Yinfei Zhou

  2. Xiangtan Maternal and Child Health Hospital, Xiangtan, 411100, China

    Tao He

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  1. Yuan Feng
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  2. Tao He
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YF and TH: designed the concept, and prepared the original draft of the manuscript. BZ, YZ, and HY: conceived and revised the manuscript. All authors have read and approved the published version of the review.

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Correspondence to Yinfei Zhou.

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Detailed information of 56 research investigating the epidemiological characteristics of HMPV in China.

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Feng, Y., He, T., Zhang, B. et al. Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review. Virol J 21, 59 (2024). https://doi.org/10.1186/s12985-024-02327-9

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Virology Journal

ISSN: 1743-422X