Avian reovirus L2 genome segment sequences and predicted structure/function of the encoded RNA-dependent RNA polymerase protein
© Xu and Coombs; licensee BioMed Central Ltd. 2008
Received: 02 December 2008
Accepted: 17 December 2008
Published: 17 December 2008
The orthoreoviruses are infectious agents that possess a genome comprised of 10 double-stranded RNA segments encased in two concentric protein capsids. Like virtually all RNA viruses, an RNA-dependent RNA polymerase (RdRp) enzyme is required for viral propagation. RdRp sequences have been determined for the prototype mammalian orthoreoviruses and for several other closely-related reoviruses, including aquareoviruses, but have not yet been reported for any avian orthoreoviruses.
We determined the L2 genome segment nucleotide sequences, which encode the RdRp proteins, of two different avian reoviruses, strains ARV138 and ARV176 in order to define conserved and variable regions within reovirus RdRp proteins and to better delineate structure/function of this important enzyme. The ARV138 L2 genome segment was 3829 base pairs long, whereas the ARV176 L2 segment was 3830 nucleotides long. Both segments were predicted to encode λB RdRp proteins 1259 amino acids in length. Alignments of these newly-determined ARV genome segments, and their corresponding proteins, were performed with all currently available homologous mammalian reovirus (MRV) and aquareovirus (AqRV) genome segment and protein sequences. There was ~55% amino acid identity between ARV λB and MRV λ3 proteins, making the RdRp protein the most highly conserved of currently known orthoreovirus proteins, and there was ~28% identity between ARV λB and homologous MRV and AqRV RdRp proteins. Predictive structure/function mapping of identical and conserved residues within the known MRV λ3 atomic structure indicated most identical amino acids and conservative substitutions were located near and within predicted catalytic domains and lining RdRp channels, whereas non-identical amino acids were generally located on the molecule's surfaces.
The ARV λB and MRV λ3 proteins showed the highest ARV:MRV identity values (~55%) amongst all currently known ARV and MRV proteins. This implies significant evolutionary constraints are placed on dsRNA RdRp molecules, particularly in regions comprising the canonical polymerase motifs and residues thought to interact directly with template and nascent mRNA. This may point the way to improved design of anti-viral agents specifically targeting this enzyme.
The avian reoviruses (ARVs) are members of the family Reoviridae, the only group of dsRNA viruses (out of seven dsRNA virus families) that infect mammals [1, 2]. The ARVs are the prototypic members of syncytia-inducing, non-enveloped viruses within the Orthoreovirus genus. This genus is divided into 3 subgroups: non-syncytia-inducing mammalian reovirus (MRV; subgroup 1; the prototype of the whole genus), avian reovirus and Nelson Bay virus (subgroup 2), and baboon reovirus (subgroup 3) . In contrast to the MRV, which are rarely associated with human pathology [2, 4–6], the ARV are significant pathogens of poultry, and cause a variety of diseases, including infectious enteritis in turkeys , viral arthritis/tenosynovitis , "pale bird" and runting-stunting syndromes , and gastroenteritis, hepatitis, myocarditis, and respiratory illness in chickens [2, 8, 10].
Like MRV, ARV is a non-enveloped virus with 10 linear double-stranded RNA gene segments surrounded by a double concentric icosahedral capsid shell (inner shell [also called core] and outer shell) of 70–80 nm diameter [11, 12]. The ARV genomic segments can be resolved into three size classes based on their electrophoretic mobilities, designated L (large), M (medium), and S (small) [11, 12]. In total, the genomic composition includes 3 large segments (Ll, L2, L3), 3 medium sized segments (Ml, M2, M3), and 4 small segments (S1, S2, S3, S4). Nine of the segments are monocistronic and encode a single different protein [11–13] while S1 is tricistronic with partially overlapping open reading frames (ORFs) that encode for three proteins [14, 15]. Although ARVs share many features with the prototypic MRVs, several notable differences exist including host range, pathogenicity, hemagglutination properties, and syncytium formation [11, 12, 16–21].
Genomic coding differences also exist between MRV and ARV. For example, although the ARV and MRV S1 genome segments encode homologous receptor-binding proteins [19, 22, 23], the ARV S1 genome segment encodes two additional ARV-specific gene products, one of which is responsible for ARV's unusual cell-cell fusion ability [14, 15, 24], whereas the MRV S1 segment encodes only one additional protein . In addition, available data [12, 26] suggest each of the homologous orthoreovirus λ-class proteins are encoded by different ARV and MRV L-class genome segments. Differences in the functional properties of homologous ARV and MRV proteins have also been reported. For example, two non-homologous dsRNA-binding proteins (the ARV σA core protein and the MRV σ3 major outer capsid protein) are predicted to regulate PKR activation [27, 28] while the ARV σA core protein displays nucleoside triphosphate phosphohydrolase (NTPase) activity , ascribed to the non-homologous MRV μ2  and λ1  core proteins. Based on these early comparative studies, it seems likely that additional analysis of ARV will continue to broaden our understanding of the Reoviridae family, possibly leading to the identification of novel features that impact on the distinct biological and pathogenic properties of ARV.
Recent advances have allowed sequence determinations of a growing number of virus isolates. Many ARV and MRV genome segment sequences have been reported. In addition, the complete genomic sequences of three prototype strains of MRV have been completed [32–34]. In contrast, sequence information from ARV isolates is more limited. While the entire complement of S-class genome segments (for example, [14, 15, 35–39]) and M-class genome segments (for example, [40, 41]) have been determined for some ARV clones, and sequence information is available for some ARV L1 and L3 genome segments [42, 43], there is, at present, no sequence information for the ARV L2 genome segment. This segment is presumed to encode for the viral RNA-dependent RNA polymerase (RdRp) protein, an essential enzyme for RNA virus replication. Thus, we determined the genomic sequences of the ARV L2 genome segments from two different strains of ARV (ARV138 and ARV176) in order to expand the available ARV sequence database, determine sequences of the ARV RdRp protein, and to delineate conserved structure/function features of this key viral-encoded enzyme.
Cells and viruses
Avian reovirus strain 138 (ARV138) and strain 176 (ARV176) are laboratory stocks. Virus clones were amplified in the continuous quail cell line QM5 in Medium 199 (Gibco) supplemented to contain 7.5% fetal calf serum (Hyclone), 2 mM glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, and 1 μg/ml amphotericin B, essentially as previously described .
Sequencing the L2 genome segment
Genomic dsRNA was extracted from amplified virus P2 stocks with phenol/chloroform . The extracted dsRNA were resolved in 10% SDS-PAGE and resolved L1, L2, and L3 segments separately excised. Individual segment gel bands were collected into microcentrifuge tubes, macerated, and incubated in 1–2 volumes of diffusion buffer (0.5 M ammonium acetate; 10 mM magnesium acetate; 1 mM EDTA, pH 8.0; 0.1% SDS) at 50°C for 30 minutes. The macerated gel pieces were pelleted by centrifugation at 10,000 × g for 1 min, supernatants were collected and dsRNA precipitated by ethanol. Each pellet was dried and resuspended in ddH2O for 3' ligation-based RT-PCR. All primers used for ligation, RT-PCR, and sequencing were synthesized by Invitrogen. An anchor primer, P-5' CTTATTTATTTGCGAGATGGTTATCATTTTAATTATCTCCATG 3'-Bio (5'-end phosphorylated and 3'-end biotin-blocked) was ligated to the 3' end of each genome segment, using T4 RNA ligase according to the manufacturer's instructions (Promega Inc., Madison, USA). Ligated products were precipitated by mixing with 1/2 volume of (30% PEG 8000 in 30 mM MgCl2), and centrifuged immediately at 10,000 × g for 30 minutes. The supernatants were removed and pellets were dried and dissolved in ddH2O for cDNA synthesis. Full-length cDNA copies of each L2 genome segment were synthesized using a primer (24-mer) complementary to the anchor primer by SuperScript™ II reverse transcriptase according to the manufacturer's instructions (Invitrogen). PCR amplification was performed using cDNA, a forward primer (i.e. primer used for RT), and a reverse primer, 5' ACCGAGGAGAGGgatgaataa 3', designed against highly conserved 3'-end nucleotide sequences of currently known consensus ARV L1 and L3 segment plus strands (shown in lower case) by Expand Long Template PCR System (Roche). PCR products used for DNA sequencing were gel purified using QIAquick® gel extraction kit according to the manufacturer's instructions (Qiagen).
DNA sequencing was performed in both directions by use of an ABI Prism BigDye Terminator v3.1 Cycle Sequencing Ready Reaction Kit (Applied Biosystems) and an Applied Biosystems Genetic Analyzer DNA Model 3100. The first two sequencing reactions were performed with the primers used for PCR amplification. Primers for subsequent reactions were designed from newly obtained sequences to completely sequence each full-length PCR product in both directions. Sequences nearer the ends of each segment were determined from PCR products that were amplified with a primer complementary to the anchor primer and an internal gene-specific primer. Sequences obtained from both directions were assembled and checked for accuracy with SeqMan® (Lasergene®, Version 7.1.0; DNASTAR, Inc.).
Sequences were compiled and analyzed using the Lasergene® software suite (Version 7.1.0; DNASTAR, Inc.) Pairwise sequence alignments were performed using the Wilbur-Lipman method  for highly divergent nucleotide sequences, the Martinez-NW method  for closely related nucleotide sequences, and the Lipman-Pearson method  for protein alignments in MegAlign® (Lasergene®). Multiple sequence alignments were performed using Clustal-W  and T-Coffee , and alignment adjustments were manually performed as needed in MegAlign®. Amino acid alignment images were adjusted in Adobe Photoshop 7.0 (Adobe®). Nucleotide compositions and protein molecular weights were calculated by DNA statistics and protein statistics, respectively, in EditSeq® (Lasergene®). Phylogenetic trees were constructed using Neighbor-Joining and tested with 1000 bootstrap replicates in MEGA version 4 .
3-D structural analyses
Molecular graphics coordinates of the mammalian reovirus (MRV) λ3 crystal structure (PDB # 1MUK; ), were manipulated with the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (; supported by NIH P41 RR-01081). Resulting images were imported into Adobe Photoshop and assembled with Adobe Illustrator (Adobe).
Nucleotide sequences used in this study
GenBank Accession Number
Genome-segment lengths, non-translated regions, and encoded proteins of ARV138 and ARV176
Molecular weight (kDa)e
(no. of bases)
(no. of bases)
Percent identities of the ARV L2 genome segments and homologous encoded proteins of MRV and Aquareovirusesa
In conclusion, we report the first sequence analysis of the avian reovirus RdRp gene and protein. The ARV λB and MRV λ3 proteins showed the highest ARV:MRV identity values (~55%) amongst currently known ARV and MRV proteins, suggesting significant evolutionary constraints are placed on dsRNA RdRp molecules, particularly in regions comprising the canonical polymerase motifs and residues thought to interact directly with template and nascent mRNA.
We thank members of our laboratory for critical reviews of this manuscript and Kolawole Opanubi for expert technical assistance. This research was supported by grant FRN-11630 from the Canadian Institutes of Health Research.
- Mertens P: The dsRNA viruses. Virus Research 2004, 101: 3-13. 10.1016/j.virusres.2003.12.002View ArticlePubMedGoogle Scholar
- Schiff LA, Nibert ML, Tyler KL: Orthoreoviruses and their replication. In Fields Virology. Edited by: Knipe DM, Howley PM. Philadelphia: Lippincott Williams & Wilkins; 2007:1853-1915.Google Scholar
- Chappell JD, Duncan R, Mertens PPC, Dermody TS: "Genus Orthoreovirus". In Virus Taxonomy Eighth Report of the International Committee on Taxonomy of Viruses. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. San Diego, CA: Elsevier Inc; 2005.Google Scholar
- Johansson PJ, Sveger T, Ahlfors K, Ekstrand J, Svensson L: Reovirus type 1 associated with meningitis. Scand J Infect Dis 1996, 28: 117-120. 10.3109/00365549609049060View ArticlePubMedGoogle Scholar
- Hermann L, Embree J, Hazelton P, Wells B, Coombs K: Reovirus type 2 isolated from cerebrospinal fluid. Ped Infect Dis J 2004, 23: 373-375. 10.1097/00006454-200404000-00026View ArticleGoogle Scholar
- Tyler KL, Barton ES, Ibach ML, Robinson C, Campbell JA, O'Donnell SM, et al.: Isolation and molecular characterization of a novel type 3 reovirus from a child with meningitis. J Infect Dis 2004, 189: 1664-1675. 10.1086/383129View ArticlePubMedGoogle Scholar
- Gershowitz A, Wooley RW: Characterization of two reoviruses isolated from turkeys with infectious enteritis. Avian Dis 1973, 17: 406-414. 10.2307/1589225View ArticlePubMedGoogle Scholar
- Olson NO: "Reovirus infections". In Diseases of poultry. Edited by: Hofstad MS. Ames, Iowa: Iowa State University Press; 1978.Google Scholar
- Kouwenhoven B, Vertommen M, Eck JHv: Runting and leg weakness in broilers: involvement of infectious factors. Vet Sci Commun 1978, 2: 253-259. 10.1007/BF02291456View ArticleGoogle Scholar
- Rosenberger JK, Olson NO: "Reovirus infections". In Diseases of poultry. Edited by: Calnek BW, Burnes MJ, Beard CW, Reid WM, Yoder HW. Ames, Iowa: Iowa State University Press; 1991.Google Scholar
- Spandidos DA, Graham AF: Physical and chemical characterization of an avian reovirus. J Virol 1976, 19: 968-976.PubMed CentralPubMedGoogle Scholar
- Benavente J, Martinez-Costas J: Avian reovirus: Structure and biology. Virus Research 2007, 123: 105-119. 10.1016/j.virusres.2006.09.005View ArticlePubMedGoogle Scholar
- Gouvea VS, Schnitzer TJ: Polymorphism of the genomic RNAs among the avian reoviruses. J Gen Virol 1982,61(Pt 1):87-91. 10.1099/0022-1317-61-1-87View ArticlePubMedGoogle Scholar
- Bodelon G, Labrada L, Martinez-Costas J, Benavente J: The avian reovirus genome segment S1 is a functionally tricistronic gene that expresses one structural and two nonstructural proteins in infected cells. Virology 2001, 290: 181-191. 10.1006/viro.2001.1159View ArticlePubMedGoogle Scholar
- Shmulevitz M, Yameen Z, Dawe S, Shou J, O'Hara D, Holmes I, et al.: Sequential partially overlapping gene arrangement in the tricistronic S1 genome segments of avian reovirus and Nelson Bay reovirus: implications for translation initiation. J Virol 2002, 76: 609-618. 10.1128/JVI.76.2.609-618.2002PubMed CentralView ArticlePubMedGoogle Scholar
- Schnitzer TJ: Protein coding assignment of the S genes of the avian reovirus S1133. Virology 1985, 141: 167-170. 10.1016/0042-6822(85)90194-1View ArticlePubMedGoogle Scholar
- Ni Y, Ramig RF: Characterization of avian reovirus-induced cell fusion: the role of viral structural proteins. Virology 1993, 194: 705-714. 10.1006/viro.1993.1311View ArticlePubMedGoogle Scholar
- Theophilos MB, Huang JA, Holmes IH: Avian reovirus sigma C protein contains a putative fusion sequence and induces fusion when expressed in mammalian cells. Virology 1995, 208: 678-684. 10.1006/viro.1995.1199View ArticlePubMedGoogle Scholar
- Martinez-Costas J, Grande A, Varela R, Garcia-Martinez C, Benavente J: Protein architecture of avian reovirus S1133 and identification of the cell attachment protein. J Virol 1997, 71: 59-64.PubMed CentralPubMedGoogle Scholar
- Jones RC: Avian reovirus infections. Rev Sci Tech 2000, 19: 614-625.PubMedGoogle Scholar
- Zhang X, Tang J, Walker SB, O'Hara D, Nibert ML, Duncan R, et al.: Structure of avian orthoreovirus virion by electron cryomicroscopy and image reconstruction. Virology 2005, 343: 25-35. 10.1016/j.virol.2005.08.002PubMed CentralView ArticlePubMedGoogle Scholar
- Weiner HL, Ault KA, Fields BN: Interaction of reovirus with cell surface receptors. I. Murine and human lymphocytes have a receptor for the hemagglutinin of reovirus type 3. J Immunol 1980, 124: 2143-2148.PubMedGoogle Scholar
- Grande A, Costas C, Benavente J: Subunit composition and conformational stability of the oligomeric form of the avian reovirus cell-attachment protein sigmaC. J Gen Virol 2002, 83: 131-139.View ArticlePubMedGoogle Scholar
- Shmulevitz M, Duncan R: A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic reoviruses. EMBO J 2000, 19: 902-912. 10.1093/emboj/19.5.902PubMed CentralView ArticlePubMedGoogle Scholar
- Munemitsu SM, Atwater JA, Samuel CE: Biosynthesis of reovirus-specified polypeptides. Molecular cDNA cloning and nucleotide sequence of the reovirus serotype 1 Lang strain bicistronic s1 mRNA which encodes the minor capsid polypeptide sigma 1a and the nonstructural polypeptide sigma 1bNS. Biochem Biophys Res Commun 1986, 140: 508-514. 10.1016/0006-291X(86)90761-8View ArticlePubMedGoogle Scholar
- Dryden KA, Coombs KM, Yeager M: The structure of orthoreoviruses. In Segmented Double-stranded RNA Viruses: Structure and Molecular Biology. Edited by: Patton JT. Horizon Press; 2008:3-25.Google Scholar
- Schiff LA, Nibert ML, Co MS, Brown EG, Fields BN: Distinct binding sites for zinc and double-stranded RNA in the reovirus outer capsid protein sigma 3. Mol Cell Biol 1988, 8: 273-283.PubMed CentralView ArticlePubMedGoogle Scholar
- Gonzalez-Lopez C, Martinez-Costas J, Esteban M, Benavente J: Evidence that avian reovirus sigmaA protein is an inhibitor of the double-stranded RNA-dependent protein kinase. J Gen Virol 2003, 84: 1629-1639. 10.1099/vir.0.19004-0View ArticlePubMedGoogle Scholar
- Yin HS, Su YP, Lee LH: Evidence of nucleotidyl phosphatase activity associated with core protein sigma A of avian reovirus S1133. Virology 2002, 293: 379-385. 10.1006/viro.2001.1292View ArticlePubMedGoogle Scholar
- Noble S, Nibert ML: Core protein mu2 is a second determinant of nucleoside triphosphatase activities by reovirus cores. J Virol 1997, 71: 7728-7735.PubMed CentralPubMedGoogle Scholar
- Bisaillon M, Bergeron J, Lemay G: Characterization of the nucleoside triphosphate phosphohydrolase and helicase activities of the reovirus lambda1 protein. J Biol Chem 1997, 272: 18298-18303. 10.1074/jbc.272.29.18298View ArticlePubMedGoogle Scholar
- Wiener JR, Bartlett JA, Joklik WK: The sequences of reovirus serotype 3 genome segments M1 and M3 encoding the minor protein mu 2 and the major nonstructural protein mu NS, respectively. Virology 1989, 169: 293-304. 10.1016/0042-6822(89)90154-2View ArticlePubMedGoogle Scholar
- Breun LA, Broering TJ, McCutcheon AM, Harrison SJ, Luongo CL, Nibert ML: Mammalian reovirus L2 gene and lambda2 core spike protein sequences and whole-genome comparisons of reoviruses type 1 Lang, type 2 Jones, and type 3 Dearing. Virology 2001, 287: 333-348. 10.1006/viro.2001.1052View ArticlePubMedGoogle Scholar
- Yin P, Keirstead ND, Broering TJ, Arnold MM, Parker JSL, Nibert ML, et al.: Comparisons of the M1 genome segments and encoded μ2 proteins of different reovirus isolates. Virol J 1(6):
- Chiu CJ, Lee LH: Cloning and nucleotide sequencing of the S4 genome segment of avian reovirus S1133. Arch Virol 1997, 142: 2515-2520. 10.1007/s007050050258View ArticlePubMedGoogle Scholar
- Duncan R: Extensive sequence divergence and phylogenetic relationships between the fusogenic and nonfusogenic orthoreoviruses: a species proposal. Virology 1999, 260: 316-328. 10.1006/viro.1999.9832View ArticlePubMedGoogle Scholar
- Liu HJ, Huang PH: Sequence and phylogenetic analysis of the sigma A-encoding gene of avian reovirus. J Virol Meth 2001, 98: 99-107. 10.1016/S0166-0934(01)00328-7View ArticleGoogle Scholar
- Kapczynski DR, Sellers HS, Simmons V, Schultz-Cherry S: Sequence analysis of the S3 gene from a turkey reovirus. Virus Genes 2002, 25: 95-100. 10.1023/A:1020130410601View ArticlePubMedGoogle Scholar
- Sellers HS, Linnemann EG, Pereira L, Kapczynski DR: Phylogenetic analysis of the sigma 2 protein gene of turkey reoviruses. Avian Dis 2004, 48: 651-657. 10.1637/7181-032304RView ArticlePubMedGoogle Scholar
- Touris-Otero F, Cortez-San Martín M, Martinez-Costas J, Benavente J: Avian reovirus morphogenesis occurs within viral factories and begins with the selective recruitment of sigma NS and lambda A to mu NS inclusions. J Mol Biol 2004, 341: 361-374. 10.1016/j.jmb.2004.06.026View ArticlePubMedGoogle Scholar
- Noad L, Shou JY, Coombs KM, Duncan R: Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function of the encoded mu proteins. Virus Research 2006, 116: 45-57. 10.1016/j.virusres.2005.08.014View ArticlePubMedGoogle Scholar
- Hsiao J, Martinez-Costas J, Benavente J, Vakharia VN: Cloning, expression, and characterization of avian reovirus guanylyltransferase. Virology 2002, 296: 288-299. 10.1006/viro.2002.1427View ArticlePubMedGoogle Scholar
- Shen PC, Chiou YF, Liu HJ, Song CH, Su YP, Lee LH: Genetic variation of the lambda A and lambda C protein encoding genes of avian reoviruses. Res Vet Sci 2007, 83: 394-402. 10.1016/j.rvsc.2007.01.002View ArticlePubMedGoogle Scholar
- Patrick M, Duncan R, Coombs KM: Generation and genetic characterization of avian reovirus temperature-sensitive mutants. Virology 2001, 284: 113-122. 10.1006/viro.2001.0915View ArticlePubMedGoogle Scholar
- Sambrook J, Fritsch EF, Maniatis T: Molecular cloning: a laboratory manual. 2nd edition. Cold Spring Harbor: Cold Spring Harbor Laboratory; 1989.Google Scholar
- Wilbur WJ, Lipman DJ: Rapid Similarity Searches of Nucleic-Acid and Protein Data Banks. Proc Natl Acad Sci (USA) 1983, 80: 726-730. 10.1073/pnas.80.3.726View ArticleGoogle Scholar
- Martinez HM: An Efficient Method for Finding Repeats in Molecular Sequences. Nucl Acids Res 1983, 11: 4629-4634. 10.1093/nar/11.13.4629PubMed CentralView ArticlePubMedGoogle Scholar
- Lipman DJ, Pearson WR: Rapid and Sensitive Protein Similarity Searches. Science 1985, 227: 1435-1441. 10.1126/science.2983426View ArticlePubMedGoogle Scholar
- Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22: 4673-4680. 10.1093/nar/22.22.4673PubMed CentralView ArticlePubMedGoogle Scholar
- Notredame C, Higgins DG, Heringa J: T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol 2000, 302: 205-217. 10.1006/jmbi.2000.4042View ArticlePubMedGoogle Scholar
- Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 2007, 24: 1596-1599. 10.1093/molbev/msm092View ArticlePubMedGoogle Scholar
- Tao Y, Farsetta DL, Nibert ML, Harrison SC: RNA synthesis in a cage – Structural studies of reovirus polymerase lambda3. Cell 2002, 111: 733-745. 10.1016/S0092-8674(02)01110-8View ArticlePubMedGoogle Scholar
- Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al.: UCSF chimera – A visualization system for exploratory research and analysis. J Comput Chem 2004, 25: 1605-1612. 10.1002/jcc.20084View ArticlePubMedGoogle Scholar
- Starnes MC, Joklik WK: Reovirus protein lambda 3 is a poly(C)-dependent poly(G) polymerase. Virology 1993, 193: 356-366. 10.1006/viro.1993.1132View ArticlePubMedGoogle Scholar
- Fang Q, Attoui H, Cantaloube JF, Biagini P, Zhu Z, de Micco P, et al.: Sequence of genome segments 1, 2, and 3 of the grass carp reovirus (Genus Aquareovirus, family Reoviridae). Biochem Biophys Res Commun 2000, 274: 762-766. 10.1006/bbrc.2000.3215View ArticlePubMedGoogle Scholar
- Bisaillon M, Lemay G: Computational sequence analysis of mammalian reovirus proteins. Virus Genes 1999, 18: 13-37. 10.1023/A:1008013117929View ArticlePubMedGoogle Scholar
- Morozov SY: A possible relationship of reovirus putative RNA polymerase to polymerases of positive-strand RNA viruses. Nucleic Acids Res 1989, 17: 5394. 10.1093/nar/17.13.5394PubMed CentralView ArticlePubMedGoogle Scholar
- Bruenn JA: Relationships Among the Positive Strand and Double-Strand Rna Viruses As Viewed Through Their Rna-Dependent Rna-Polymerases. Nucl Acids Res 1991, 19: 217-226. 10.1093/nar/19.2.217PubMed CentralView ArticlePubMedGoogle Scholar
- Bruenn JA: A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucl Acids Res 2003, 31: 1821-1829. 10.1093/nar/gkg277PubMed CentralView ArticlePubMedGoogle Scholar
- Kim J, Tao Y, Reinisch KM, Harrison SC, Nibert ML: Orthoreovirus and Aquareovirus core proteins: conserved enzymatic surfaces, but not protein-protein interfaces. Virus Research 2004, 101: 15-28. 10.1016/j.virusres.2003.12.003View ArticlePubMedGoogle Scholar
- Guardado-Calvo P, Vazquez-Iglesias L, Martinez-Costas J, Llamas-Saiz AL, Schoehn G, Fox GC, et al.: Crystal structure of the avian reovirus inner capsid protein sigmaA. J Virol 2008, 82: 11208-11216. 10.1128/JVI.00733-08PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang X, Walker SB, Chipman PR, Nibert ML, Baker TS: Reovirus polymerase lambda 3 localized by cryo-electron microscopy of virions at a resolution of 7.6 angstrom. Nature Structural Biology 2003, 10: 1011-1018. 10.1038/nsb1009PubMed CentralView ArticlePubMedGoogle Scholar
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