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Sub-genomic replicon and virus-like particles of Omsk hemorrhagic fever virus

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Abstract

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis serocomplex of flaviviruses, and causes hemorrhagic disease in humans. To investigate the molecular mechanisms involved in OHFV pathogenesis, we constructed several subgenomic OHFV replicons containing large deletions in the structural region. Replicon RNA was introduced into BHK cells by transfection and the production of viral proteins was monitored by IFA. GFP and luciferase genes were inserted into the OHFV replicon, and these reporter genes were expressed in cells harboring replicating replicon RNA. OHFV replicons were packaged into single-round infectious virus-like particles (VLPs) by sequential transfection with replicon RNA and a plasmid expressing the viral structural proteins. Reporter genes were expressed in cells infected with VLPs, and the infection was inhibited by neutralizing antibodies. These replicon and VLP systems will be useful tools for investigating the molecular mechanism of OHFV pathogenicity.

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References

  1. Aberle JH, Aberle SW, Kofler RM, Mandl CW (2005) Humoral and cellular immune response to RNA immunization with flavivirus replicons derived from tick-borne encephalitis virus. J Virol 79:15107–15113

    Article  PubMed  CAS  Google Scholar 

  2. Bredenbeek PJ, Frolov I, Rice CM, Schlesinger S (1993) Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs. J Virol 67:6439–6446

    PubMed  CAS  Google Scholar 

  3. Buchen-Osmond C (2003) 00.026.0.01.046.02. Tick-borne encephalitis virus group. In: ICTVdB—the Universal Virus Database, version 3. In: Buchen-Osmond C (ed) ICTVdB Management, Columbia University, New York

  4. Burke DS, Monath TP (2001) Flaviviruses. In: Knipe DM, Howley PM (eds) Fields’ Virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1043–1125

    Google Scholar 

  5. Chambers TJ, Hahn CS, Galler R, Rice CM (1990) Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688

    Article  PubMed  CAS  Google Scholar 

  6. Gehrke R, Ecker M, Aberle SW, Allison SL, Heinz FX, Mandl CW (2003) Incorporation of tick-borne encephalitis virus replicons into virus-like particles by a packaging cell line. J Virol 77:8924–8933

    Article  PubMed  CAS  Google Scholar 

  7. Gehrke R, Heinz FX, Davis NL, Mandl CW (2005) Heterologous gene expression by infectious and replicon vectors derived from tick-borne encephalitis virus and direct comparison of this flavivirus system with an alphavirus replicon. J Gen Virol 86:1045–1053

    Article  PubMed  CAS  Google Scholar 

  8. Gritsun TS, Venugopal K, Zanotto PM, Mikhailov MV, Sall AA, Holmes EC, Polkinghorne I, Frolova TV, Pogodina VV, Lashkevich VA, Gould EA (1997) Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Res 49:27–39

    Article  PubMed  CAS  Google Scholar 

  9. Hayasaka D, Yoshii K, Ueki T, Iwasaki T, Takashima I (2004) Sub-genomic replicons of Tick-borne encephalitis virus. Arch Virol 149:1245–1256

    Article  PubMed  CAS  Google Scholar 

  10. Hoenninger VM, Rouha H, Orlinger KK, Miorin L, Marcello A, Kofler RM, Mandl CW (2008) Analysis of the effects of alterations in the tick-borne encephalitis virus 3′-noncoding region on translation and RNA replication using reporter replicons. Virology 377:419–430

    Article  PubMed  CAS  Google Scholar 

  11. Holbrook MR, Shope RE, Barrett AD (2004) Use of recombinant E protein domain III-based enzyme-linked immunosorbent assays for differentiation of tick-borne encephalitis serocomplex flaviviruses from mosquito-borne flaviviruses. J Clin Microbiol 42:4101–4110

    Article  PubMed  CAS  Google Scholar 

  12. Holbrook MR, Aronson JF, Campbell GA, Jones S, Feldmann H, Barrett AD (2005) An animal model for the tickborne flavivirus–Omsk hemorrhagic fever virus. J Infect Dis 191:100–108

    Article  PubMed  Google Scholar 

  13. Ishikawa T, Widman DG, Bourne N, Konishi E, Mason PW (2008) Construction and evaluation of a chimeric pseudoinfectious virus vaccine to prevent Japanese encephalitis. Vaccine 26:2772–2781

    Article  PubMed  CAS  Google Scholar 

  14. Jones CT, Patkar CG, Kuhn RJ (2005) Construction and applications of yellow fever virus replicons. Virology 331:247–259

    Article  PubMed  CAS  Google Scholar 

  15. Kharitonova NN, Leonov YA (1985) Omsk hemorrhagic fever. Trans. S. Korzelska. Amerind Publishing, New Delhi

    Google Scholar 

  16. Khromykh AA, Westaway EG (1997) Subgenomic replicons of the flavivirus Kunjin: construction and applications. J Virol 71:1497–1505

    PubMed  CAS  Google Scholar 

  17. Khromykh AA, Varnavski AN, Westaway EG (1998) Encapsidation of the flavivirus Kunjin replicon RNA by using a complementation system providing Kunjin virus structural proteins in trans. J Virol 72:5967–5977

    PubMed  CAS  Google Scholar 

  18. Kofler RM, Aberle JH, Aberle SW, Allison SL, Heinz FX, Mandl CW (2004) Mimicking live flavivirus immunization with a noninfectious RNA vaccine. Proc Natl Acad Sci USA 101:1951–1956

    Article  PubMed  CAS  Google Scholar 

  19. Lin D, Li L, Dick D, Shope RE, Feldmann H, Barrett AD, Holbrook MR (2003) Analysis of the complete genome of the tick-borne flavivirus Omsk hemorrhagic fever virus. Virology 313:81–90

    Article  PubMed  CAS  Google Scholar 

  20. Lindenbach BD, Rice CM (2001) Flaviviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields’ Virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 991–1041

    Google Scholar 

  21. Mason PW, Bezborodova SV, Henry TM (2002) Identification and characterization of a cis-acting replication element (cre) adjacent to the internal ribosome entry site of foot-and-mouth disease virus. J Virol 76:9686–9694

    Article  PubMed  CAS  Google Scholar 

  22. Miorin L, Maiuri P, Hoenninger VM, Mandl CW, Marcello A (2008) Spatial and temporal organization of tick-borne encephalitis flavivirus replicated RNA in living cells. Virology 379:64–77

    Article  PubMed  CAS  Google Scholar 

  23. Molenkamp R, Kooi EA, Lucassen MA, Greve S, Thijssen JC, Spaan WJ, Bredenbeek PJ (2003) Yellow fever virus replicons as an expression system for hepatitis C virus structural proteins. J Virol 77:1644–1648

    Article  PubMed  CAS  Google Scholar 

  24. Moser C, Stettler P, Tratschin JD, Hofmann MA (1999) Cytopathogenic and noncytopathogenic RNA replicons of classical swine fever virus. J Virol 73:7787–7794

    PubMed  CAS  Google Scholar 

  25. Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199

    Article  PubMed  CAS  Google Scholar 

  26. Ojwang JO, Ali S, Smee DF, Morrey JD, Shimasaki CD, Sidwell RW (2005) Broad-spectrum inhibitor of viruses in the Flaviviridae family. Antiviral Res 68:49–55

    Article  PubMed  CAS  Google Scholar 

  27. Pang X, Zhang M, Dayton AI (2001) Development of Dengue virus type 2 replicons capable of prolonged expression in host cells. BMC Microbiol 1:18

    Article  PubMed  CAS  Google Scholar 

  28. Percy N, Barclay WS, Garcia-Sastre A, Palese P (1994) Expression of a foreign protein by influenza A virus. J Virol 68:4486–4492

    PubMed  CAS  Google Scholar 

  29. Pierson TC, Sanchez MD, Puffer BA, Ahmed AA, Geiss BJ, Valentine LE, Altamura LA, Diamond MS, Doms RW (2006) A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection. Virology 346:53–65

    Article  PubMed  CAS  Google Scholar 

  30. Pijlman GP, Suhrbier A, Khromykh AA (2006) Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for protein production, vaccine and gene therapy applications. Expert Opin Biol Ther 6:135–145

    Article  PubMed  CAS  Google Scholar 

  31. Proutski V, Gould EA, Holmes EC (1997) Secondary structure of the 3′ untranslated region of flaviviruses: similarities and differences. Nucleic Acids Res 25:1194–1202

    Article  PubMed  CAS  Google Scholar 

  32. Puig-Basagoiti F, Deas TS, Ren P, Tilgner M, Ferguson DM, Shi PY (2005) High-throughput assays using a luciferase-expressing replicon, virus-like particles, and full-length virus for West Nile virus drug discovery. Antimicrob Agents Chemother 49:4980–4988

    Article  PubMed  CAS  Google Scholar 

  33. Raju R, Subramaniam SV, Hajjou M (1995) Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors. J Virol 69:7391–7401

    PubMed  CAS  Google Scholar 

  34. Rauscher S, Flamm C, Mandl CW, Heinz FX, Stadler PF (1997) Secondary structure of the 3′-noncoding region of flavivirus genomes: comparative analysis of base pairing probabilities. RNA 3:779–791

    PubMed  CAS  Google Scholar 

  35. Reimann I, Semmler I, Beer M (2007) Packaged replicons of bovine viral diarrhea virus are capable of inducing a protective immune response. Virology 366:377–386

    Article  PubMed  CAS  Google Scholar 

  36. Ruggli N, Tratschin JD, Mittelholzer C, Hofmann MA (1996) Nucleotide sequence of classical swine fever virus strain Alfort/187 and transcription of infectious RNA from stably cloned full-length cDNA. J Virol 70:3478–3487

    PubMed  CAS  Google Scholar 

  37. Scholle F, Girard YA, Zhao Q, Higgs S, Mason PW (2004) Trans-Packaged West Nile virus-like particles: infectious properties in vitro and in infected mosquito vectors. J Virol 78:11605–11614

    Article  PubMed  CAS  Google Scholar 

  38. Shi PY, Tilgner M, Lo MK (2002) Construction and characterization of subgenomic replicons of New York strain of West Nile virus. Virology 296:219–233

    Article  PubMed  CAS  Google Scholar 

  39. Westaway EG, Mackenzie JM, Khromykh AA (2003) Kunjin RNA replication and applications of Kunjin replicons. Adv Virus Res 59:99–140

    Article  PubMed  CAS  Google Scholar 

  40. Widman DG, Ishikawa T, Fayzulin R, Bourne N, Mason PW (2008) Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system. Vaccine 26:2762–2771

    Article  PubMed  CAS  Google Scholar 

  41. Yoshii K, Konno A, Goto A, Nio J, Obara M, Ueki T, Hayasaka D, Mizutani T, Kariwa H, Takashima I (2004) Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol 85:3049–3058

    Article  PubMed  CAS  Google Scholar 

  42. Yoshii K, Hayasaka D, Goto A, Kawakami K, Kariwa H, Takashima I (2005) Packaging the replicon RNA of the Far-Eastern subtype of tick-borne encephalitis virus into single-round infectious particles; development of a heterologous gene delivery system. Vaccine (in press)

  43. Yoshii K, Goto A, Kawakami K, Kariwa H, Takashima I (2008) Construction and application of chimeric virus-like particles of tick-borne encephalitis virus and mosquito-borne Japanese encephalitis virus. J Gen Virol 89:200–211

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. P. W. Mason of UTMB for providing the pACNR plasmid. This work was supported by Overseas Assignment Program for Japanese Researchers in Research into Emerging and Re-emerging Infectious Diseases from The Japan Health Sciences Foundation (KY) and the a Western Regional Center of Excellence Career Development Award (U54AI057156) (MH).

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Correspondence to Michael R. Holbrook.

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Yoshii, K., Holbrook, M.R. Sub-genomic replicon and virus-like particles of Omsk hemorrhagic fever virus. Arch Virol 154, 573–580 (2009). https://doi.org/10.1007/s00705-009-0345-5

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  • DOI: https://doi.org/10.1007/s00705-009-0345-5

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