1887

Abstract

A full-length infectious cDNA clone of the genotype 1 Korean avian hepatitis E virus (avian HEV) (pT11-aHEV-K) was constructed and its infectivity and pathogenicity were investigated in leghorn male hepatoma (LMH) chicken cells and broiler breeders. We demonstrated that capped RNA transcripts from the pT11-aHEV-K clone were translation competent when transfected into LMH cells and infectious when injected intrahepatically into the livers of chickens. Gross and microscopic pathological lesions underpinned the avian HEV infection and helped characterize its pathogenicity in broiler breeder chickens. The avian HEV genome contains a hypervariable region (HVR) in ORF1. To demonstrate the utility of the avian HEV infectious clone, several mutants with various deletions in and beyond the known HVR were derived from the pT11-aHEV-K clone. The HVR-deletion mutants were replication competent in LMH cells, although the deletion mutants extending beyond the known HVR were non-viable. By using the pT11-aHEV-K infectious clone as the backbone, an avian HEV luciferase reporter replicon and HVR-deletion mutant replicons were also generated. The luciferase assay results of the reporter replicon and its mutants support the data obtained from the infectious clone and its derived mutants. To further determine the effect of HVR deletion on virus replication, the capped RNA transcripts from the wild-type pT11-aHEV-K clone and its mutants were injected intrahepatically into chickens. The HVR-deletion mutants that were translation competent in LMH cells displayed in chickens an attenuation phenotype of avian HEV infectivity, suggesting that the avian HEV HVR is important in modulating the virus infectivity and pathogenicity.

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2015-05-01
2019-10-20
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References

  1. Arankalle V. A. , Chadha M. S. , Tsarev S. A. , Emerson S. U. , Risbud A. R. , Banerjee K. , Purcell R. H. . ( 1994; ). Seroepidemiology of water-borne hepatitis in India and evidence for a third enterically-transmitted hepatitis agent. . Proc Natl Acad Sci U S A 91:, 3428–3432. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bányai K. , Tóth A. G. , Ivanics E. , Glávits R. , Szentpáli-Gavallér K. , Dán A. . ( 2012; ). Putative novel genotype of avian hepatitis E virus, Hungary, 2010. . Emerg Infect Dis 18:, 1365–1368. [CrossRef] [PubMed]
    [Google Scholar]
  3. Bilic I. , Jaskulska B. , Basic A. , Morrow C. J. , Hess M. . ( 2009; ). Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes. . J Gen Virol 90:, 863–873. [CrossRef] [PubMed]
    [Google Scholar]
  4. Billam P. , Huang F. F. , Sun Z. F. , Pierson F. W. , Duncan R. B. , Elvinger F. , Guenette D. K. , Toth T. E. , Meng X. J. . ( 2005; ). Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens. . J Virol 79:, 3429–3437. [CrossRef] [PubMed]
    [Google Scholar]
  5. Billam P. , LeRoith T. , Pudupakam R. S. , Pierson F. W. , Duncan R. B. , Meng X. J. . ( 2009; ). Comparative pathogenesis in specific-pathogen-free chickens of two strains of avian hepatitis E virus recovered from a chicken with Hepatitis-Splenomegaly syndrome and from a clinically healthy chicken. . Vet Microbiol 139:, 253–261. [CrossRef] [PubMed]
    [Google Scholar]
  6. Bliska J. . ( 1996; ). How pathogens exploit interactions mediated by SH3 domains. . Chem Biol 3:, 7–11. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cao D. , Meng X. J. . ( 2012; ). Molecular biology and replication of hepatitis E virus. . Emerg Microbes Infect 1:, e17. [CrossRef]
    [Google Scholar]
  8. Cossaboom C. M. , Córdoba L. , Dryman B. A. , Meng X. J. . ( 2011; ). Hepatitis E virus in rabbits, Virginia, USA. . Emerg Infect Dis 17:, 2047–2049. [CrossRef] [PubMed]
    [Google Scholar]
  9. Emerson S. U. , Purcell R. H. . ( 2003; ). Hepatitis E virus. . Rev Med Virol 13:, 145–154. [CrossRef] [PubMed]
    [Google Scholar]
  10. Graff J. , Nguyen H. , Yu C. , Elkins W. R. , St Claire M. , Purcell R. H. , Emerson S. U. . ( 2005; ). The open reading frame 3 gene of hepatitis E virus contains a cis-reactive element and encodes a protein required for infection of macaques. . J Virol 79:, 6680–6689. [CrossRef] [PubMed]
    [Google Scholar]
  11. Guo H. , Zhou E. M. , Sun Z. F. , Meng X. J. , Halbur P. G. . ( 2006; ). Identification of B-cell epitopes in the capsid protein of avian hepatitis E virus (avian HEV) that are common to human and swine HEVs or unique to avian HEV. . J Gen Virol 87:, 217–223. [CrossRef] [PubMed]
    [Google Scholar]
  12. Haqshenas G. , Shivaprasad H. L. , Woolcock P. R. , Read D. H. , Meng X. J. . ( 2001; ). Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. . J Gen Virol 82:, 2449–2462.[PubMed] [CrossRef]
    [Google Scholar]
  13. Haqshenas G. , Huang F. F. , Fenaux M. , Guenette D. K. , Pierson F. W. , Larsen C. T. , Shivaprasad H. L. , Toth T. E. , Meng X. J. . ( 2002; ). The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus. . J Gen Virol 83:, 2201–2209.[PubMed] [CrossRef]
    [Google Scholar]
  14. Hsu I. W. , Tsai H. J. . ( 2014; ). Avian hepatitis E virus in chickens, Taiwan, 2013. . Emerg Infect Dis 20:, 149–151. [CrossRef] [PubMed]
    [Google Scholar]
  15. Huang F. F. , Sun Z. F. , Emerson S. U. , Purcell R. H. , Shivaprasad H. L. , Pierson F. W. , Toth T. E. , Meng X. J. . ( 2004; ). Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV. . J Gen Virol 85:, 1609–1618. [CrossRef] [PubMed]
    [Google Scholar]
  16. Huang Y. W. , Haqshenas G. , Kasorndorkbua C. , Halbur P. G. , Emerson S. U. , Meng X. J. . ( 2005; a). Capped RNA transcripts of full-length cDNA clones of swine hepatitis E virus are replication competent when transfected into Huh7 cells and infectious when intrahepatically inoculated into pigs. . J Virol 79:, 1552–1558. [CrossRef] [PubMed]
    [Google Scholar]
  17. Huang F. F. , Pierson F. W. , Toth T. E. , Meng X. J. . ( 2005; b). Construction and characterization of infectious cDNA clones of a chicken strain of hepatitis E virus (HEV), avian HEV. . J Gen Virol 86:, 2585–2593. [CrossRef] [PubMed]
    [Google Scholar]
  18. Johne R. , Dremsek P. , Reetz J. , Heckel G. , Hess M. , Ulrich R. G. . ( 2014; ). Hepeviridae: an expanding family of vertebrate viruses. . Infect Genet Evol 27:, 212–229. [CrossRef] [PubMed]
    [Google Scholar]
  19. Koonin E. V. , Gorbalenya A. E. , Purdy M. A. , Rozanov M. N. , Reyes G. R. , Bradley D. W. . ( 1992; ). Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. . Proc Natl Acad Sci U S A 89:, 8259–8263. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kwon H. M. , LeRoith T. , Pudupakam R. S. , Pierson F. W. , Huang Y. W. , Dryman B. A. , Meng X. J. . ( 2011; ). Construction of an infectious cDNA clone of avian hepatitis E virus (avian HEV) recovered from a clinically healthy chicken in the United States and characterization of its pathogenicity in specific-pathogen-free chickens. . Vet Microbiol 147:, 310–319. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kwon H. M. , Sung H. W. , Meng X. J. . ( 2012; ). Serological prevalence, genetic identification, and characterization of the first strains of avian hepatitis E virus from chickens in Korea. . Virus Genes 45:, 237–245. [CrossRef] [PubMed]
    [Google Scholar]
  22. Macdonald A. , Mazaleyrat S. , McCormick C. , Street A. , Burgoyne N. J. , Jackson R. M. , Cazeaux V. , Shelton H. , Saksela K. , Harris M. . ( 2005; ). Further studies on hepatitis C virus NS5A-SH3 domain interactions: identification of residues critical for binding and implications for viral RNA replication and modulation of cell signalling. . J Gen Virol 86:, 1035–1044. [CrossRef] [PubMed]
    [Google Scholar]
  23. Marek A. , Bilic I. , Prokofieva I. , Hess M. . ( 2010; ). Phylogenetic analysis of avian hepatitis E virus samples from European and Australian chicken flocks supports the existence of a different genus within the Hepeviridae comprising at least three different genotypes. . Vet Microbiol 145:, 54–61. [CrossRef] [PubMed]
    [Google Scholar]
  24. Meng X. J. . ( 2010; a). Hepatitis E virus: animal reservoirs and zoonotic risk. . Vet Microbiol 140:, 256–265. [CrossRef] [PubMed]
    [Google Scholar]
  25. Meng X. J. . ( 2010; b). Recent advances in Hepatitis E virus. . J Viral Hepat 17:, 153–161. [CrossRef] [PubMed]
    [Google Scholar]
  26. Meng X. J. , Shivaprasad H. . ( 2013; ). Avian hepatitis E virus infections. . In Diseases of Poultry, pp. 494–500. Edited by Swayne D. E. , Glisson J. , McDougald L. R. , Nolan L. K. , Suarez D. L. , Nair V. L. . . Hoboken, NJ:: Wiley-Blackwell;.
    [Google Scholar]
  27. Meng X. J. , Halbur P. G. , Shapiro M. S. , Govindarajan S. , Bruna J. D. , Mushahwar I. K. , Purcell R. H. , Emerson S. U. . ( 1998; ). Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. . J Virol 72:, 9714–9721.[PubMed]
    [Google Scholar]
  28. Meng X. J. , Anderson D. A. , Arankalle V. A. , Emerson S. U. , Harrison T. J. , Jameel S. , Okamoto H. . ( 2012; ). Hepeviridae. . In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, pp. 1021–1028. Edited by King A. M. Q. , Adams M. J. , Carstens E. B. , Lefkowita E. J. . . London:: Elsevier/Academic Press;.
    [Google Scholar]
  29. Okamoto H. . ( 2011; ). Hepatitis E virus cell culture models. . Virus Res 161:, 65–77. [CrossRef] [PubMed]
    [Google Scholar]
  30. Panda S. K. , Ansari I. H. , Durgapal H. , Agrawal S. , Jameel S. . ( 2000; ). The in vitro-synthesized RNA from a cDNA clone of hepatitis E virus is infectious. . J Virol 74:, 2430–2437. [CrossRef] [PubMed]
    [Google Scholar]
  31. Pavio N. , Meng X. J. , Renou C. . ( 2010; ). Zoonotic hepatitis E: animal reservoirs and emerging risks. . Vet Res 41:, 46. [CrossRef] [PubMed]
    [Google Scholar]
  32. Payne C. J. , Ellis T. M. , Plant S. L. , Gregory A. R. , Wilcox G. E. . ( 1999; ). Sequence data suggests big liver and spleen disease virus (BLSV) is genetically related to hepatitis E virus. . Vet Microbiol 68:, 119–125. [CrossRef] [PubMed]
    [Google Scholar]
  33. Pudupakam R. S. , Huang Y. W. , Opriessnig T. , Halbur P. G. , Pierson F. W. , Meng X. J. . ( 2009; ). Deletions of the hypervariable region (HVR) in open reading frame 1 of hepatitis E virus do not abolish virus infectivity: evidence for attenuation of HVR deletion mutants in vivo. . J Virol 83:, 384–395. [CrossRef] [PubMed]
    [Google Scholar]
  34. Pudupakam R. S. , Kenney S. P. , Córdoba L. , Huang Y. W. , Dryman B. A. , Leroith T. , Pierson F. W. , Meng X. J. . ( 2011; ). Mutational analysis of the hypervariable region of hepatitis E virus reveals its involvement in the efficiency of viral RNA replication. . J Virol 85:, 10031–10040. [CrossRef] [PubMed]
    [Google Scholar]
  35. Purdy M. A. , Lara J. , Khudyakov Y. E. . ( 2012; ). The hepatitis E virus polyproline region is involved in viral adaptation. . PLoS ONE 7:, e35974. [CrossRef] [PubMed]
    [Google Scholar]
  36. Riddell M. A. , Li F. , Anderson D. A. . ( 2000; ). Identification of immunodominant and conformational epitopes in the capsid protein of hepatitis E virus by using monoclonal antibodies. . J Virol 74:, 8011–8017. [CrossRef] [PubMed]
    [Google Scholar]
  37. Shivaprasad, H. L. & Woolcock, P. R. (1995). Necrohemorrhagic hepatitis in broiler breeders. Proceedings of the Western Poultry Diseases Conference, Sacramento, CA, USA. p. 6.
  38. Smith D. B. , Vanek J. , Ramalingam S. , Johannessen I. , Templeton K. , Simmonds P. . ( 2012; ). Evolution of the hepatitis E virus hypervariable region. . J Gen Virol 93:, 2408–2418. [CrossRef] [PubMed]
    [Google Scholar]
  39. Smith D. B. , Simmonds P. , Jameel S. , Emerson S. U. , Harrison T. J. , Meng X. J. , Okamoto H. , Van der Poel W. H. , Purdy M. A. . International Committee on Taxonomy of Viruses Hepeviridae Study Group ( 2014; ). Consensus proposals for classification of the family Hepeviridae. . J Gen Virol 95:, 2223–2232. [CrossRef] [PubMed]
    [Google Scholar]
  40. Sun Z. F. , Larsen C. T. , Huang F. F. , Billam P. , Pierson F. W. , Toth T. E. , Meng X. J. . ( 2004; ). Generation and infectivity titration of an infectious stock of avian hepatitis E virus (HEV) in chickens and cross-species infection of turkeys with avian HEV. . J Clin Microbiol 42:, 2658–2662. [CrossRef] [PubMed]
    [Google Scholar]
  41. Troxler S. , Pać K. , Prokofieva I. , Liebhart D. , Chodakowska B. , Furmanek D. , Hess M. . ( 2014; ). Subclinical circulation of avian hepatitis E virus within a multiple-age rearing and broiler breeder farm indicates persistence and vertical transmission of the virus. . Avian Pathol 43:, 310–318. [CrossRef] [PubMed]
    [Google Scholar]
  42. Van der Poel W. H. . ( 2014; ). Food and environmental routes of Hepatitis E virus transmission. . Curr Opin Virol 4:, 91–96. [CrossRef] [PubMed]
    [Google Scholar]
  43. Yamada K. , Takahashi M. , Hoshino Y. , Takahashi H. , Ichiyama K. , Nagashima S. , Tanaka T. , Okamoto H. . ( 2009; a). ORF3 protein of hepatitis E virus is essential for virion release from infected cells. . J Gen Virol 90:, 1880–1891. [CrossRef] [PubMed]
    [Google Scholar]
  44. Yamada K. , Takahashi M. , Hoshino Y. , Takahashi H. , Ichiyama K. , Tanaka T. , Okamoto H. . ( 2009; b). Construction of an infectious cDNA clone of hepatitis E virus strain JE03-1760F that can propagate efficiently in cultured cells. . J Gen Virol 90:, 457–462. [CrossRef] [PubMed]
    [Google Scholar]
  45. Yazaki Y. , Mizuo H. , Takahashi M. , Nishizawa T. , Sasaki N. , Gotanda Y. , Okamoto H. . ( 2003; ). Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. . J Gen Virol 84:, 2351–2357. [CrossRef] [PubMed]
    [Google Scholar]
  46. Zhao Q. , Zhou E. M. , Dong S. W. , Qiu H. K. , Zhang L. , Hu S. B. , Zhao F. F. , Jiang S. J. , Sun Y. N. . ( 2010; ). Analysis of avian hepatitis E virus from chickens, China. . Emerg Infect Dis 16:, 1469–1472. [CrossRef] [PubMed]
    [Google Scholar]
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