1887

Journal of General Virology header logo

Volume 96, Issue 6

Construction and characterization of an infectious cDNA clone of rat hepatitis E virus Free

Abstract

Rat hepatitis E virus (HEV) is related to human HEV and has been detected in wild rats worldwide. Here, the complete genome of rat HEV strain R63/DEU/2009 was cloned downstream of the T7 RNA polymerase promoter and capped genomic RNA generated by transcription was injected into nude rats. Rat HEV RNA could be detected in serum and faeces of rats injected intrahepatically, but not in those injected intravenously. Rat HEV RNA-positive faecal suspension was intravenously inoculated into nude rats and Wistar rats leading to rat HEV RNA detection in serum and faeces of nude rats, and to seroconversion in Wistar rats. In addition, rat HEV was isolated in PLC/PRF/5 cells from the rat HEV RNA-positive faecal suspension of nude rats and then passaged. The cell culture supernatant was infectious for nude rats. Genome analysis identified nine point mutations of the cell-culture-passaged virus in comparison with the originally cloned rat HEV genome. The results indicated that infectious rat HEV could be generated from the cDNA clone. As rats are widely used and well-characterized laboratory animals, studies on genetically engineered rat HEV may provide novel insights into organ tropism, replication and excretion kinetics as well as immunological changes induced by hepeviruses.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000072
2015-06-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/6/1320.html?itemId=/content/journal/jgv/10.1099/vir.0.000072&mimeType=html&fmt=ahah

References

  1. Córdoba L., Feagins A. R., Opriessnig T., Cossaboom C. M., Dryman B. A., Huang Y. W., Meng X. J. 2012; Rescue of a genotype 4 human hepatitis E virus from cloned cDNA and characterization of intergenotypic chimeric viruses in cultured human liver cells and in pigs. J Gen Virol 93:2183–2194 [View Article][PubMed]
     [Google Scholar]
  2. Cossaboom C. M., Córdoba L., Sanford B. J., Piñeyro P., Kenney S. P., Dryman B. A., Wang Y., Meng X. J. 2012; Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States. J Gen Virol 93:1687–1695 [View Article][PubMed]
     [Google Scholar]
  3. Cossaboom C. M., Huang Y. W., Yugo D. M., Kenney S. P., Piñeyro P., Matzinger S. R., Heffron C. L., Pierson F. W., Meng X. J. 2014; RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are infectious in rabbits. J Gen Virol doi:10.1099/vir.0.071407-0 (Epub ahead of print) [View Article][PubMed]
     [Google Scholar]
  4. Dremsek P., Wenzel J. J., Johne R., Ziller M., Hofmann J., Groschup M. H., Werdermann S., Mohn U., Dorn S. et al. 2012; Seroprevalence study in forestry workers from eastern Germany using novel genotype 3- and rat hepatitis E virus-specific immunoglobulin G ELISAs. Med Microbiol Immunol (Berl) 201:189–200 [View Article][PubMed]
     [Google Scholar]
  5. Emerson S. U., Zhang M., Meng X.-J., Nguyen H., St Claire M., Govindarajan S., Huang Y. K., Purcell R. H. 2001; Recombinant hepatitis E virus genomes infectious for primates: importance of capping and discovery of a cis-reactive element. Proc Natl Acad Sci U S A 98:15270–15275 [View Article][PubMed]
     [Google Scholar]
  6. Guan D., Li W., Su J., Fang L., Takeda N., Wakita T., Li T. C., Ke C. 2013; Asian musk shrew as a reservoir of rat hepatitis E virus, China. Emerg Infect Dis 19:1341–1343 [View Article][PubMed]
     [Google Scholar]
  7. Hoenen T., Groseth A., de Kok-Mercado F., Kuhn J. H., Wahl-Jensen V. 2011; Minigenomes, transcription and replication competent virus-like particles and beyond: reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses. Antiviral Res 91:195–208 [View Article][PubMed]
     [Google Scholar]
  8. Huang F. F., Pierson F. W., Toth T. E., Meng X. J. 2005a). Construction and characterization of infectious cDNA clones of a chicken strain of hepatitis E virus (HEV), avian HEV. J Gen Virol 86:2585–2593 [View Article][PubMed]
     [Google Scholar]
  9. Huang Y. W., Haqshenas G., Kasorndorkbua C., Halbur P. G., Emerson S. U., Meng X. J. 2005b). 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 [View Article][PubMed]
     [Google Scholar]
  10. Jirintai S., Tanggis, Mulyanto, Suparyatmo J. B., Takahashi M., Kobayashi T., Nagashima S., Nishizawa T., Okamoto H. 2014; Rat hepatitis E virus derived from wild rats (Rattus rattus) propagates efficiently in human hepatoma cell lines. Virus Res 185:92–102 [View Article][PubMed]
     [Google Scholar]
  11. Johne R., Plenge-Bönig A., Hess M., Ulrich R. G., Reetz J., Schielke A. 2010a). Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J Gen Virol 91:750–758 [View Article][PubMed]
     [Google Scholar]
  12. Johne R., Heckel G., Plenge-Bönig A., Kindler E., Maresch C., Reetz J., Schielke A., Ulrich R. G. 2010b). Novel hepatitis E virus genotype in Norway rats, Germany. Emerg Infect Dis 16:1452–1455 [View Article][PubMed]
     [Google Scholar]
  13. Johne R., Dremsek P., Reetz J., Heckel G., Hess M., Ulrich R. G. 2014a). Hepeviridae: an expanding family of vertebrate viruses. Infect Genet Evol 27:212–229 [View Article][PubMed]
     [Google Scholar]
  14. Johne R., Reetz J., Ulrich R. G., Machnowska P., Sachsenröder J., Nickel P., Hofmann J. 2014b). An ORF1-rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture. J Viral Hepat 21:447–456 [View Article][PubMed]
     [Google Scholar]
  15. Krumbholz A., Joel S., Neubert A., Dremsek P., Dürrwald R., Johne R., Hlinak A., Walther M., Lange J. et al. 2013; Age-related and regional differences in the prevalence of hepatitis E virus-specific antibodies in pigs in Germany. Vet Microbiol 167:394–402 [View Article][PubMed]
     [Google Scholar]
  16. 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 [View Article][PubMed]
     [Google Scholar]
  17. Li T.-C., Yoshimatsu K., Yasuda S. P., Arikawa J., Koma T., Kataoka M., Ami Y., Suzaki Y., Mai T. Q. et al. 2011; Characterization of self-assembled virus-like particles of rat hepatitis E virus generated by recombinant baculoviruses. J Gen Virol 92:2830–2837 [View Article][PubMed]
     [Google Scholar]
  18. Li W., Guan D., Su J., Takeda N., Wakita T., Li T. C., Ke C. W. 2013a). High prevalence of rat hepatitis E virus in wild rats in China. Vet Microbiol 165:275–280 [View Article][PubMed]
     [Google Scholar]
  19. Li T. C., Yoshizaki S., Ami Y., Suzaki Y., Yasuda S. P., Yoshimatsu K., Arikawa J., Takeda N., Wakita T. 2013b). Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses. Vet Microbiol 163:54–61 [View Article][PubMed]
     [Google Scholar]
  20. Mulyanto S., Suparyatmo J. B., Andayani I. G., Khalid, Takahashi M., Ohnishi H., Jirintai S., Nagashima S., Nishizawa T., Okamoto H. 2014; Marked genomic heterogeneity of rat hepatitis E virus strains in Indonesia demonstrated on a full-length genome analysis. Virus Res 179:102–112 [View Article][PubMed]
     [Google Scholar]
  21. Okamoto H. 2011; Hepatitis E virus cell culture models. Virus Res 161:65–77 [View Article][PubMed]
     [Google Scholar]
  22. 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 [View Article][PubMed]
     [Google Scholar]
  23. Purcell R. H., Engle R. E., Rood M. P., Kabrane-Lazizi Y., Nguyen H. T., Govindarajan S., St Claire M., Emerson S. U. 2011; Hepatitis E virus in rats, Los Angeles, California, USA. Emerg Infect Dis 17:2216–2222 [View Article][PubMed]
     [Google Scholar]
  24. Raj V. S., Smits S. L., Pas S. D., Provacia L. B., Moorman-Roest H., Osterhaus A. D., Haagmans B. L. 2012; Novel hepatitis E virus in ferrets, the Netherlands. Emerg Infect Dis 18:1369–1370 [View Article][PubMed]
     [Google Scholar]
  25. 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 [View Article][PubMed]
     [Google Scholar]
  26. Stobart C. C., Moore M. L. 2014; RNA virus reverse genetics and vaccine design. Viruses 6:2531–2550 [View Article][PubMed]
     [Google Scholar]
  27. Yamada K., Takahashi M., Hoshino Y., Takahashi H., Ichiyama K., Tanaka T., Okamoto H. 2009; 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 [View Article][PubMed]
     [Google Scholar]
  28. Ye S., Evans J. G., Stambas J. 2014; Influenza reverse genetics: dissecting immunity and pathogenesis. Expert Rev Mol Med 16:e2 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000072
Loading
Construction and characterization of an infectious cDNA clone of rat hepatitis E virus
J. Gen. Virol. 96, 1320 (2015); https://doi.org/10.1099/vir.0.000072
/content/journal/jgv/10.1099/vir.0.000072
/content/journal/jgv/10.1099/vir.0.000072
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF

Most cited Most Cited RSS feed

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