1887

Abstract

The cell line IPLB-LD-652Y, derived from the gypsy moth ( L.), is routinely used to study interactions between viruses and insect hosts. Here we report the full genome sequence and biological characteristics of a small RNA virus, designated Lymantria dispar iflavirus 1 (LdIV1), that was discovered to persistently infect IPLB-LD-652Y. LdIV1 belongs to the genus . LdIV1 formed icosahedral particles of approx. 30 nm in diameter and contained a 10 044 nt polyadenylated, positive-sense RNA genome encoding a predicted polyprotein of 2980 aa. LdIV1 was induced by a viral suppressor of RNA silencing, suggesting that acute infection is restricted by RNA interference (RNAi). We detected LdIV1 in all tested tissues of gypsy-moth larvae and adults, but the virus was absent from other -derived cell lines. We confirmed LdIV1 infectivity in two of these cell lines (IPLB-LD-652 and IPLB-LdFB). Our results provide a novel system to explore persistent infections in lepidopterans and a new model for the study of iflaviruses, a rapidly expanding group of viruses, many of which covertly infect their hosts.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.067710-0
2014-10-01
2019-11-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/10/2285.html?itemId=/content/journal/jgv/10.1099/vir.0.067710-0&mimeType=html&fmt=ahah

References

  1. Alberts B. , Johnson A. , Lewis J. , Raff M. , Roberts K. , Walter P. . ( 2002; ). Molecular Biology of the Cell, , 4th edn.. New York:: Garland Science;.
    [Google Scholar]
  2. Altschul S. F. , Madden T. L. , Schäffer A. A. , Zhang J. , Zhang Z. , Miller W. , Lipman D. J. . ( 1997; ). Gapped blast and psi-blast: a new generation of protein database search programs. . Nucleic Acids Res 25:, 3389–3402. [CrossRef] [PubMed]
    [Google Scholar]
  3. Altschul S. F. , Wootton J. C. , Gertz E. M. , Agarwala R. , Morgulis A. , Schäffer A. A. , Yu Y. K. . ( 2005; ). Protein database searches using compositionally adjusted substitution matrices. . FEBS J 272:, 5101–5109. [CrossRef] [PubMed]
    [Google Scholar]
  4. Blom N. , Hansen J. , Brunak S. , Blaas D. . ( 1996; ). Cleavage site analysis in picornaviral polyproteins: discovering cellular targets by neural networks. . Protein Sci 5:, 2203–2216. [CrossRef] [PubMed]
    [Google Scholar]
  5. Cavener D. R. , Ray S. C. . ( 1991; ). Eukaryotic start and stop translation sites. . Nucleic Acids Res 19:, 3185–3192. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen Y. P. , Becnel J. J. , Valles S. M. . ( 2012a; ). RNA Viruses Infecting Pest Insects. . In Insect Pathology, , 2nd edn., pp. 133–170. Edited by Vega F. E. , Kaya H. K. . . San Diego:: Academic Press;. [CrossRef]
    [Google Scholar]
  7. Chen Y. P. , Nakashima N. , Christian P. D. , Bakonyi T. , Bonning B. C. , Valles S. M. , Lightner D. . ( 2012b; ). Family Dicistroviridae . . In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, pp. 840–845. Edited by King A. M. Q. , Adams M. J. , Carstens E. B. , Lefkowitz E. J. . . London:: Elsevier Academic;.
    [Google Scholar]
  8. Choi J. Y. , Kim Y.-S. , Wang Y. , Shin S. W. , Kim I. , Tao X. Y. , Liu Q. , Roh J. Y. , Kim J. S. , Je Y. H. . ( 2012; ). Complete genome sequence of a novel picorna-like virus isolated from Spodoptera exigua . . J Asia Pac Entomol 15:, 259–263. [CrossRef]
    [Google Scholar]
  9. de Miranda J. R. , Genersch E. . ( 2010; ). Deformed wing virus. . J Invertebr Pathol 103: (Suppl 1), S48–S61. [CrossRef] [PubMed]
    [Google Scholar]
  10. de Miranda J. R. , Dainat B. , Locke B. , Cordoni G. , Berthoud H. , Gauthier L. , Neumann P. , Budge G. E. , Ball B. V. , Stoltz D. B. . ( 2010; ). Genetic characterization of slow bee paralysis virus of the honeybee (Apis mellifera L.). . J Gen Virol 91:, 2524–2530. [CrossRef] [PubMed]
    [Google Scholar]
  11. Domingo E. , Sheldon J. , Perales C. . ( 2012; ). Viral quasispecies evolution. . Microbiol Mol Biol Rev 76:, 159–216. [CrossRef] [PubMed]
    [Google Scholar]
  12. Drugmand J.-C. , Schneider Y.-J. , Agathos S. N. . ( 2012; ). Insect cells as factories for biomanufacturing. . Biotechnol Adv 30:, 1140–1157. [CrossRef] [PubMed]
    [Google Scholar]
  13. Felsenstein J. . ( 1985; ). Confidence limits on phylogenies: an approach using the bootstrap. . Evolution 39:, 783–791. [CrossRef]
    [Google Scholar]
  14. Garner K. J. , Slavicek J. M. . ( 1999; ). Identification of a non-LTR retrotransposon from the gypsy moth. . Insect Mol Biol 8:, 231–242. [CrossRef] [PubMed]
    [Google Scholar]
  15. Geng P. , Li W. , Lin L. , de Miranda J. R. , Emrich S. , An L. , Terenius O. . ( 2014; ). Genetic characterization of a novel Iflavirus associated with vomiting disease in the Chinese oak silkmoth Antheraea pernyi . . PLoS ONE 9:, e92107. [CrossRef] [PubMed]
    [Google Scholar]
  16. Ghosh R. C. , Ball B. V. , Willcocks M. M. , Carter M. J. . ( 1999; ). The nucleotide sequence of sacbrood virus of the honey bee: an insect picorna-like virus. . J Gen Virol 80:, 1541–1549.[PubMed]
    [Google Scholar]
  17. Goic B. , Saleh M. C. . ( 2012; ). Living with the enemy: viral persistent infections from a friendly viewpoint. . Curr Opin Microbiol 15:, 531–537. [CrossRef] [PubMed]
    [Google Scholar]
  18. Goic B. , Vodovar N. , Mondotte J. A. , Monot C. , Frangeul L. , Blanc H. , Gausson V. , Vera-Otarola J. , Cristofari G. , Saleh M. C. . ( 2013; ). RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila . . Nat Immunol 14:, 396–403. [CrossRef] [PubMed]
    [Google Scholar]
  19. Goodwin R. H. , Tompkins G. J. , McCawley P. . ( 1978; ). Gypsy moth cell lines divergent in viral susceptibility. I. Culture and identification. . In Vitro 14:, 485–494. [CrossRef] [PubMed]
    [Google Scholar]
  20. Gorbalenya A. E. , Donchenko A. P. , Blinov V. M. , Koonin E. V. . ( 1989; ). Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold. . FEBS Lett 243:, 103–114. [CrossRef] [PubMed]
    [Google Scholar]
  21. Guzo D. , Dougherty E. M. , Lynn D. E. , Braun S. K. , Weiner R. M. . ( 1991; ). Changes in macromolecular synthesis of gypsy moth cell line IPLB-Ld652Y induced by Autographa californica nuclear polyhedrosis virus infection. . J Gen Virol 72:, 1021–1029. [CrossRef] [PubMed]
    [Google Scholar]
  22. Harrison R. L. , Sparks W. O. , Bonning B. C. . ( 2010; ). Autographa californica multiple nucleopolyhedrovirus ODV-E56 envelope protein is required for oral infectivity and can be substituted functionally by Rachiplusia ou multiple nucleopolyhedrovirus ODV-E56. . J Gen Virol 91:, 1173–1182. [CrossRef] [PubMed]
    [Google Scholar]
  23. He B. , Li Z. , Yang F. , Zheng J. , Feng Y. , Guo H. , Li Y. , Wang Y. , Su N. . & other authors ( 2013; ). Virome profiling of bats from Myanmar by metagenomic analysis of tissue samples reveals more novel mammalian viruses. . PLoS ONE 8:, e61950. [CrossRef] [PubMed]
    [Google Scholar]
  24. Hulo C. , de Castro E. , Masson P. , Bougueleret L. , Bairoch A. , Xenarios I. , Le Mercier P. . ( 2011; ). ViralZone: a knowledge resource to understand virus diversity. . Nucleic Acids Res 39: (Database issue), D576–D582. [CrossRef] [PubMed]
    [Google Scholar]
  25. Isawa H. , Asano S. , Sahara K. , Iizuka T. , Bando H. . ( 1998; ). Analysis of genetic information of an insect picorna-like virus, infectious flacherie virus of silkworm: evidence for evolutionary relationships among insect, mammalian and plant picorna(-like) viruses. . Arch Virol 143:, 127–143. [CrossRef] [PubMed]
    [Google Scholar]
  26. Jarvis D. L. , Weinkauf C. , Guarino L. A. . ( 1996; ). Immediate-early baculovirus vectors for foreign gene expression in transformed or infected insect cells. . Protein Expr Purif 8:, 191–203. [CrossRef] [PubMed]
    [Google Scholar]
  27. Johansson H. , Dhaygude K. , Lindström S. , Helanterä H. , Sundström L. , Trontti K. . ( 2013; ). A metatranscriptomic approach to the identification of microbiota associated with the ant Formica exsecta . . PLoS ONE 8:, e79777. [CrossRef] [PubMed]
    [Google Scholar]
  28. Jovel J. , Schneemann A. . ( 2011; ). Molecular characterization of Drosophila cells persistently infected with Flock House virus. . Virology 419:, 43–53. [CrossRef] [PubMed]
    [Google Scholar]
  29. Kazuhiko Y. , Shinji T. , Tosihiko H. . ( 1996; ). Replication of a small isometric virus in cultured Lymantria dispar (Lepidoptera: Lymantriidae) cells. . Appl Entomol Zool (Jpn) 31:, 637–641.
    [Google Scholar]
  30. Killington R. A. , Stokes A. , Hierholzer J. C. . ( 1996; ). PEG precipitation. . In Virology Methods Manual, pp. 73–74. Edited by Mahy B. W. J. , Kangro H. O. . . London:: Academic Press;. [CrossRef]
    [Google Scholar]
  31. Kim M. K. , Sisson G. , Stoltz D. . ( 1996; ). Ichnovirus infection of an established gypsy moth cell line. . J Gen Virol 77:, 2321–2328. [CrossRef] [PubMed]
    [Google Scholar]
  32. Koonin E. V. , Dolja V. V. , Morris T. J. . ( 1993; ). Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. . Crit Rev Biochem Mol Biol 28:, 375–430. [CrossRef] [PubMed]
    [Google Scholar]
  33. Kozak M. . ( 1999; ). Initiation of translation in prokaryotes and eukaryotes. . Gene 234:, 187–208. [CrossRef] [PubMed]
    [Google Scholar]
  34. Kuhn J. H. , Jahrling P. B. . ( 2010; ). Clarification and guidance on the proper usage of virus and virus species names. . Arch Virol 155:, 445–453. [CrossRef] [PubMed]
    [Google Scholar]
  35. Lanzi G. , de Miranda J. R. , Boniotti M. B. , Cameron C. E. , Lavazza A. , Capucci L. , Camazine S. M. , Rossi C. . ( 2006; ). Molecular and biological characterization of deformed wing virus of honeybees (Apis mellifera L.). . J Virol 80:, 4998–5009. [CrossRef] [PubMed]
    [Google Scholar]
  36. Léry X. , Fédière G. , Taha A. , Salah M. , Giannotti J. . ( 1997; ). A new small RNA virus persistently infecting an established cell line of Galleria mellonella, induced by a heterologous infection. . J Invertebr Pathol 69:, 7–13. [CrossRef] [PubMed]
    [Google Scholar]
  37. Léry X. , Zeddam J. L. , Giannotti J. , Abol-Ela S. . ( 1998; ). Evidence for two small viruses persistently infecting established cell lines of Phthorimaea operculella, deriving from embryos of the potato tuber moth. . New Microbiol 21:, 81–85.[PubMed]
    [Google Scholar]
  38. Li T. C. , Scotti P. D. , Miyamura T. , Takeda N. . ( 2007; ). Latent infection of a new alphanodavirus in an insect cell line. . J Virol 81:, 10890–10896.[CrossRef]
    [Google Scholar]
  39. Lu J. , Hu Y. , Hu L. , Zong S. , Cai D. , Wang J. , Yu H. , Zhang J. . ( 2007; ). Ectropis obliqua picorna-like virus IRES-driven internal initiation of translation in cell systems derived from different origins. . J Gen Virol 88:, 2834–2838. [CrossRef] [PubMed]
    [Google Scholar]
  40. Lynn D. E. . ( 2001; ). Novel techniques to establish new insect cell lines. . In Vitro Cell Dev Biol Anim 37:, 319–321. [CrossRef] [PubMed]
    [Google Scholar]
  41. Lynn D. E. . ( 2006; ). Lepidopteran cell lines after long-term culture in alternative media: comparison of growth rates and baculovirus replication. . In Vitro Cell Dev Biol Anim 42:, 149–152. [CrossRef] [PubMed]
    [Google Scholar]
  42. Lynn D. E. , Dougherty E. M. , McClintock J. T. , Loeb M. . ( 1988; ). Development of cell lines from various tissues of Lepidoptera. . In Invertebrate and Fish Tissue Culture: Proceedings of the Seventh International Conference on Invertebrate and Fish Tissue Culture, pp. 239–242. Edited by Y. Kuroda . , E. Kurstak . & K. Maramorosch . . Tokyo:: Japan Scientific Societies Press;.[CrossRef]
    [Google Scholar]
  43. Marchler-Bauer A. , Lu S. , Anderson J. B. , Chitsaz F. , Derbyshire M. K. , DeWeese-Scott C. , Fong J. H. , Geer L. Y. , Geer R. C. . & other authors ( 2011; ). CDD: a Conserved Domain Database for the functional annotation of proteins. . Nucleic Acids Res 39: (Database issue), D225–D229. [CrossRef] [PubMed]
    [Google Scholar]
  44. Marchler-Bauer A. , Zheng C. , Chitsaz F. , Derbyshire M. K. , Geer L. Y. , Geer R. C. , Gonzales N. R. , Gwadz M. , Hurwitz D. I. . & other authors ( 2013; ). CDD: conserved domains and protein three-dimensional structure. . Nucleic Acids Res 41: (Database issue), D348–D352. [CrossRef] [PubMed]
    [Google Scholar]
  45. McClintock J. T. , Dougherty E. M. , Weiner R. M. . ( 1986; ). Semipermissive replication of a nuclear polyhedrosis virus of Autographa californica in a gypsy moth cell line. . J Virol 57:, 197–204.[PubMed]
    [Google Scholar]
  46. McIntosh A. H. , Grasela J. J. , Popham H. J. R. . ( 2005; ). AcMNPV in permissive, semipermissive, and nonpermissive cell lines from arthropoda. . In Vitro Cell Dev Biol Anim 41:, 298–304. [CrossRef] [PubMed]
    [Google Scholar]
  47. McKelvey T. A. , Lynn D. E. , Gundersen-Rindal D. , Guzo D. , Stoltz D. A. , Guthrie K. P. , Taylor P. B. , Dougherty E. M. . ( 1996; ). Transformation of gypsy moth (Lymantria dispar) cell lines by infection with Glyptapanteles indiensis polydnavirus. . Biochem Biophys Res Commun 225:, 764–770. [CrossRef] [PubMed]
    [Google Scholar]
  48. Millán-Leiva A. , Jakubowska A. K. , Ferré J. , Herrero S. . ( 2012; ). Genome sequence of SeIV-1, a novel virus from the Iflaviridae family infective to Spodoptera exigua . . J Invertebr Pathol 109:, 127–133. [CrossRef] [PubMed]
    [Google Scholar]
  49. Moore B. A. . ( 2009; ). Lymantria dispar. . In Global Review of Forest Pest and Diseases: A Thematic Study Prepared in the Framework of the Global Forest Resources Assessment 2005, pp. 99–102. Edited by Moore B. A. , Allard G. . . Rome:: Food and Agriculture Organization of The United Nations;.
    [Google Scholar]
  50. Murakami R. , Suetsugu Y. , Kobayashi T. , Nakashima N. . ( 2013; ). The genome sequence and transmission of an iflavirus from the brown planthopper, Nilaparvata lugens . . Virus Res 176:, 179–187. [CrossRef] [PubMed]
    [Google Scholar]
  51. Murakami R. , Suetsugu Y. , Nakashima N. . ( 2014; ). Complete genome sequences of two iflaviruses from the brown planthopper, Nilaparvata lugens . . Arch Virol 159:, 585–588. [CrossRef] [PubMed]
    [Google Scholar]
  52. Nayak A. , Berry B. , Tassetto M. , Kunitomi M. , Acevedo A. , Deng C. , Krutchinsky A. , Gross J. , Antoniewski C. , Andino R. . ( 2010; ). Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila . . Nat Struct Mol Biol 17:, 547–554. [CrossRef] [PubMed]
    [Google Scholar]
  53. Oliveira D. C. , Hunter W. B. , Ng J. , Desjardins C. A. , Dang P. M. , Werren J. H. . ( 2010; ). Data mining cDNAs reveals three new single stranded RNA viruses in Nasonia (Hymenoptera: Pteromalidae). . Insect Mol Biol 19: (Suppl 1), 99–107. [CrossRef] [PubMed]
    [Google Scholar]
  54. Ongus J. R. , Peters D. , Bonmatin J. M. , Bengsch E. , Vlak J. M. , van Oers M. M. . ( 2004; ). Complete sequence of a picorna-like virus of the genus Iflavirus replicating in the mite Varroa destructor . . J Gen Virol 85:, 3747–3755. [CrossRef] [PubMed]
    [Google Scholar]
  55. Ongus J. R. , Roode E. C. , Pleij C. W. , Vlak J. M. , van Oers M. M. . ( 2006; ). The 5′ non-translated region of Varroa destructor virus 1 (genus Iflavirus): structure prediction and IRES activity in Lymantria dispar cells. . J Gen Virol 87:, 3397–3407. [CrossRef] [PubMed]
    [Google Scholar]
  56. Perera O. P. , Snodgrass G. L. , Allen K. C. , Jackson R. E. , Becnel J. J. , O’Leary P. F. , Luttrell R. G. . ( 2012; ). The complete genome sequence of a single-stranded RNA virus from the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois). . J Invertebr Pathol 109:, 11–19. [CrossRef] [PubMed]
    [Google Scholar]
  57. Pfeifer T. A. , Ring M. , Grigliatti T. A. . ( 2000; ). Identification and analysis of Lydia, a LTR retrotransposon from Lymantria dispar . . Insect Mol Biol 9:, 349–356. [CrossRef] [PubMed]
    [Google Scholar]
  58. Reineke A. , Asgari S. . ( 2005; ). Presence of a novel small RNA-containing virus in a laboratory culture of the endoparasitic wasp Venturia canescens (Hymenoptera: Ichneumonidae). . J Insect Physiol 51:, 127–135. [CrossRef] [PubMed]
    [Google Scholar]
  59. Rivers T. M. . ( 1937; ). Viruses and Koch’s postulates. . J Bacteriol 33:, 1–12.[PubMed]
    [Google Scholar]
  60. Rueckert R. R. , Wimmer E. . ( 1984; ). Systematic nomenclature of picornavirus proteins. . J Virol 50:, 957–959.[PubMed]
    [Google Scholar]
  61. Ryabov E. V. . ( 2007; ). A novel virus isolated from the aphid Brevicoryne brassicae with similarity to Hymenoptera picorna-like viruses. . J Gen Virol 88:, 2590–2595. [CrossRef] [PubMed]
    [Google Scholar]
  62. Ryan M. D. , Flint M. . ( 1997; ). Virus-encoded proteinases of the picornavirus super-group. . J Gen Virol 78:, 699–723.[PubMed]
    [Google Scholar]
  63. Saitou N. , Nei M. . ( 1987; ). The neighbor-joining method: a new method for reconstructing phylogenetic trees. . Mol Biol Evol 4:, 406–425.[PubMed]
    [Google Scholar]
  64. Sharov A. A. , Leonard D. , Liebhold A. M. , Roberts E. A. , Dickerson W. . ( 2002; ). “Slow The Spread”: A national program to contain the gypsy moth. . J Forest 100:, 30–35.
    [Google Scholar]
  65. Smith G. , Macias-Muñoz A. , Briscoe A. D. . ( 2014; ). Genome sequence of a novel iflavirus from mRNA sequencing of the butterfly Heliconius erato . . Genome Announc 2:, e00398-14. [CrossRef] [PubMed]
    [Google Scholar]
  66. Sparks M. E. , Gundersen-Rindal D. E. . ( 2011; ). The Lymantria dispar IPLB-Ld652Y cell line transcriptome comprises diverse virus-associated transcripts. . Viruses 3:, 2339–2350. [CrossRef] [PubMed]
    [Google Scholar]
  67. Sparks M. E. , Gundersen-Rindal D. E. , Harrison R. L. . ( 2013; ). Complete genome sequence of a novel iflavirus from the transcriptome of Halyomorpha halys, the brown marmorated stink bug. . Genome Announc 1:, e00910-13. [CrossRef] [PubMed]
    [Google Scholar]
  68. Summers M. D. , Smith G. E. . ( 1987; ). A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures. College Station, TX:: Department of Entomology Texas Agricultural Experiment Station and Texas A&M University College Station;.
    [Google Scholar]
  69. Tamura K. , Peterson D. , Peterson N. , Stecher G. , Nei M. , Kumar S. . ( 2011; ). mega5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. . Mol Biol Evol 28:, 2731–2739. [CrossRef] [PubMed]
    [Google Scholar]
  70. Vaughn J. L. , Goodwin R. H. , Tompkins G. J. , McCawley P. . ( 1977; ). The establishment of two cell lines from the insect Spodoptera frugiperda (Lepidoptera; Noctuidae). . In Vitro 13:, 213–217. [CrossRef] [PubMed]
    [Google Scholar]
  71. Wang X. , Zhang J. , Lu J. , Yi F. , Liu C. , Hu Y. . ( 2004; ). Sequence analysis and genomic organization of a new insect picorna-like virus, Ectropis obliqua picorna-like virus, isolated from Ectropis obliqua . . J Gen Virol 85:, 1145–1151. [CrossRef] [PubMed]
    [Google Scholar]
  72. Winter J. , Hall R. L. , Moyer R. W. . ( 1995; ). The effect of inhibitors on the growth of the entomopoxvirus from Amsacta moorei in Lymantria dispar (gypsy moth) cells. . Virology 211:, 462–473. [CrossRef] [PubMed]
    [Google Scholar]
  73. Wu C. Y. , Lo C. F. , Huang C. J. , Yu H. T. , Wang C. H. . ( 2002; ). The complete genome sequence of Perina nuda picorna-like virus, an insect-infecting RNA virus with a genome organization similar to that of the mammalian picornaviruses. . Virology 294:, 312–323. [CrossRef] [PubMed]
    [Google Scholar]
  74. Ye S. , Xia H. J. , Dong C. , Cheng Z. Y. , Xia X. L. , Zhang J. M. , Zhou X. , Hu Y. Y. . ( 2012; ). Identification and characterization of iflavirus 3C-like protease processing activities. . Virology 428:, 136–145. [CrossRef] [PubMed]
    [Google Scholar]
  75. Zuckerkandl E. , Pauling L. . ( 1965; ). Evolutionary divergence and convergence in proteins. . In Evolving Genes and Proteins, pp. 97–166. Edited by Bryson V. , Vogel H. J. . . New York:: Academic Press;. [CrossRef]
    [Google Scholar]
  76. Zuker M. . ( 2003; ). Mfold web server for nucleic acid folding and hybridization prediction. . Nucleic Acids Res 31:, 3406–3415. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.067710-0
Loading
/content/journal/jgv/10.1099/vir.0.067710-0
Loading

Data & Media loading...

Supplements

Supplementary Data 

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error