1887

Abstract

dsRNA and 5′-triphosphate RNA are considered critical activators of the innate immune response because of their interaction with pattern recognition receptors. It has been reported that no dsRNA is detected in negative-sense RNA virus-infected cells and that Hantaan virus (HTNV) genomic RNA bears a 5′ monophosphate group. In this paper we examine the 5′ termini of genomic RNAs of and dsRNA production by two major groups of Old World hantaviruses. No detectable amounts of dsRNA were found in infected cells. Also, the genomic RNAs of these hantaviruses bear a 5′ monophosphate group and therefore are unable to trigger interferon induction. Taken together with the earlier data on HTNV, these results suggest that in addition to the dsRNA and genomic RNA, which may be only minimally involved in the induction of innate immunity, other cellular signalling pathways may also be involved and that these await further investigation.

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2011-05-01
2019-10-22
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References

  1. Ank N. , Paludan S. R. . ( 2009; ). Type III IFNs: new layers of complexity in innate antiviral immunity. . Biofactors 35:, 82–87. [CrossRef] [PubMed]
    [Google Scholar]
  2. Baum A. , García-Sastre A. . ( 2010; ). Induction of type I interferon by RNA viruses: cellular receptors and their substrates. . Amino Acids 38:, 1283–1299. [CrossRef] [PubMed]
    [Google Scholar]
  3. Bonin M. , Oberstrass J. , Lukacs N. , Ewert K. , Oesterschulze E. , Kassing R. , Nellen W. . ( 2000; ). Determination of preferential binding sites for anti-dsRNA antibodies on double-stranded RNA by scanning force microscopy. . RNA 6:, 563–570. [CrossRef] [PubMed]
    [Google Scholar]
  4. Garcin D. , Lezzi M. , Dobbs M. , Elliott R. M. , Schmaljohn C. , Kang C. Y. , Kolakofsky D. . ( 1995; ). The 5′ ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign mechanism for the initiation of RNA synthesis. . J Virol 69:, 5754–5762.[PubMed]
    [Google Scholar]
  5. Geimonen E. , Neff S. , Raymond T. , Kocer S. S. , Gavrilovskaya I. N. , Mackow E. R. . ( 2002; ). Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses. . Proc Natl Acad Sci U S A 99:, 13837–13842. [CrossRef] [PubMed]
    [Google Scholar]
  6. Habjan M. , Andersson I. , Klingström J. , Schümann M. , Martin A. , Zimmermann P. , Wagner V. , Pichlmair A. , Schneider U. et al. ( 2008; ). Processing of genome 5′ termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. . PLoS ONE 3:, e2032. [CrossRef] [PubMed]
    [Google Scholar]
  7. Handke W. , Oelschlegel R. , Franke R. , Krüger D. H. , Rang A. . ( 2009; ). Hantaan virus triggers TLR3-dependent innate immune responses. . J Immunol 182:, 2849–2858. [CrossRef] [PubMed]
    [Google Scholar]
  8. Hornung V. , Ellegast J. , Kim S. , Brzózka K. , Jung A. , Kato H. , Poeck H. , Akira S. , Conzelmann K. K. et al. ( 2006; ). 5′-Triphosphate RNA is the ligand for RIG-I. . Science 314:, 994–997. [CrossRef] [PubMed]
    [Google Scholar]
  9. Jääskeläinen K. M. , Kaukinen P. , Minskaya E. S. , Plyusnina A. , Vapalahti O. , Elliott R. M. , Weber F. , Vaheri A. , Plyusnin A. . ( 2007; ). Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. . J Med Virol 79:, 1527–1536. [CrossRef] [PubMed]
    [Google Scholar]
  10. Kolakofsky D. , Hacker D. . ( 1991; ). Bunyavirus RNA synthesis: genome transcription and replication. . Curr Top Microbiol Immunol 169:, 143–159.[PubMed]
    [Google Scholar]
  11. Koyama S. , Ishii K. J. , Coban C. , Akira S. . ( 2008; ). Innate immune response to viral infection. . Cytokine 43:, 336–341. [CrossRef] [PubMed]
    [Google Scholar]
  12. Kraus A. A. , Raftery M. J. , Giese T. , Ulrich R. , Zawatzky R. , Hippenstiel S. , Suttorp N. , Krüger D. H. , Schönrich G. . ( 2004; ). Differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses. . J Virol 78:, 6143–6150. [CrossRef] [PubMed]
    [Google Scholar]
  13. Lee H. W. , van der Groen G. . ( 1989; ). Hemorrhagic fever with renal syndrome. . Prog Med Virol 36:, 62–102.[PubMed]
    [Google Scholar]
  14. Lukács N. . ( 1994; ). Detection of virus infection in plants and differentiation between coexisting viruses by monoclonal antibodies to double-stranded RNA. . J Virol Methods 47:, 255–272. [CrossRef] [PubMed]
    [Google Scholar]
  15. Luthra P. , Sun D. , Silverman R. H. , He B. . ( 2011; ). Activation of IFN-β expression by a viral mRNA through RNase L and MDA5. . Proc Natl Acad Sci U S A 108:, 2118–2123. [CrossRef] [PubMed]
    [Google Scholar]
  16. Mackenzie J. . ( 2005; ). Wrapping things up about virus RNA replication. . Traffic 6:, 967–977. [CrossRef] [PubMed]
    [Google Scholar]
  17. Malley J. P. , Ballester N. A. , Margolin A. B. , Linden K. G. , Motidi A. , Bolton J. R. , Grozes G. , Laine J. M. , Janex M. L. . ( 2004; ). Inactivation of pathogens with innovative UV technologies. AWWARF, Denver CO, USA. . :, . [CrossRef] [PubMed]
    [Google Scholar]
  18. Marcus P. I. , Sekellick M. J. . ( 1977; ). Defective interfering particles with covalently linked [+/−] RNA induce interferon. . Nature 266:, 815–819. [CrossRef] [PubMed]
    [Google Scholar]
  19. Overby A. K. , Popov V. L. , Niedrig M. , Weber F. . ( 2010; ). Tick-borne encephalitis virus delays interferon induction and hides its double-stranded RNA in intracellular membrane vesicles. . J Virol 84:, 8470–8483. [CrossRef] [PubMed]
    [Google Scholar]
  20. Peters C. J. , Khan A. S. . ( 2002; ). Hantavirus pulmonary syndrome: the new American hemorrhagic fever. . Clin Infect Dis 34:, 1224–1231. [CrossRef] [PubMed]
    [Google Scholar]
  21. Pichlmair A. , Schulz O. , Tan C. P. , Näslund T. I. , Liljeström P. , Weber F. , Reis e Sousa C. . ( 2006; ). RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. . Science 314:, 997–1001. [CrossRef] [PubMed]
    [Google Scholar]
  22. Plumet S. , Herschke F. , Bourhis J. M. , Valentin H. , Longhi S. , Gerlier D. . ( 2007; ). Cytosolic 5′-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. . PLoS ONE 2:, e279. [CrossRef] [PubMed]
    [Google Scholar]
  23. Plyusnin A. . ( 2002; ). Genetics of hantaviruses: implications to taxonomy. . Arch Virol 147:, 665–682. [CrossRef] [PubMed]
    [Google Scholar]
  24. Plyusnin A. , Morzunov S. P. . ( 2001; ). Virus evolution and genetic diversity of hantaviruses and their rodent hosts. . Curr Top Microbiol Immunol 256:, 47–75.[PubMed]
    [Google Scholar]
  25. Plyusnin A. , Vapalahti O. , Vaheri A. . ( 1996; ). Hantaviruses: genome structure, expression and evolution. . J Gen Virol 77:, 2677–2687. [CrossRef] [PubMed]
    [Google Scholar]
  26. Prescott J. , Ye C. , Sen G. , Hjelle B. . ( 2005; ). Induction of innate immune response genes by Sin Nombre hantavirus does not require viral replication. . J Virol 79:, 15007–15015. [CrossRef] [PubMed]
    [Google Scholar]
  27. Prescott J. B. , Hall P. R. , Bondu-Hawkins V. S. , Ye C. , Hjelle B. . ( 2007; ). Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry. . J Immunol 179:, 1796–1802.[PubMed] [CrossRef]
    [Google Scholar]
  28. Prescott J. , Hall P. , Acuna-Retamar M. , Ye C. , Wathelet M. G. , Ebihara H. , Feldmann H. , Hjelle B. . ( 2010; ). New World hantaviruses activate IFNλ production in type I IFN-deficient Vero E6 cells. . PLoS ONE 5:, e11159. [CrossRef] [PubMed]
    [Google Scholar]
  29. Rehwinkel J. , Tan C. P. , Goubau D. , Schulz O. , Pichlmair A. , Bier K. , Robb N. , Vreede F. , Barclay W. , Fodor E. . ( 2010; ). RIG-I detects viral genomic RNA during negative-strand RNA virus infection. . Cell 140:, 397–408. [CrossRef] [PubMed]
    [Google Scholar]
  30. Richardson S. J. , Willcox A. , Hilton D. A. , Tauriainen S. , Hyoty H. , Bone A. J. , Foulis A. K. , Morgan N. G. . ( 2010; ). Use of antisera directed against dsRNA to detect viral infections in formalin-fixed paraffin-embedded tissue. . J Clin Virol 49:, 180–185. [CrossRef] [PubMed]
    [Google Scholar]
  31. Samanta M. , Iwakiri D. , Kanda T. , Imaizumi T. , Takada K. . ( 2006; ). EB virus-encoded RNAs are recognized by RIG-I and activate signaling to induce type I IFN. . EMBO J 25:, 4207–4214. [CrossRef] [PubMed]
    [Google Scholar]
  32. Schönborn J. , Oberstrass J. , Breyel E. , Tittgen J. , Schumacher J. , Lukacs N. . ( 1991; ). Monoclonal antibodies to double-stranded RNA as probes of RNA structure in crude nucleic acid extracts. . Nucleic Acids Res 19:, 2993–3000. [CrossRef] [PubMed]
    [Google Scholar]
  33. Siu R. W. , Fragkoudis R. , Simmonds P. , Donald C. L. , Chase-Topping M. E. , Barry G. , Attarzadeh-Yazdi G. , Rodriguez-Andres J. , Nash A. A. et al. ( 2010; ). Antiviral RNA interference responses induced by Semliki Forest virus infection of mosquito cells: characterization, origin and frequency-dependent functions of viRNAs. . J Virol 85:, 2907–2917. [CrossRef] [PubMed]
    [Google Scholar]
  34. Spiropoulou C. F. , Albariño C. G. , Ksiazek T. G. , Rollin P. E. . ( 2007; ). Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling. . J Virol 81:, 2769–2776. [CrossRef] [PubMed]
    [Google Scholar]
  35. tenOever B. R. , Servant M. J. , Grandvaux N. , Lin R. , Hiscott J. . ( 2002; ). Recognition of the measles virus nucleocapsid as a mechanism of IRF-3 activation. . J Virol 76:, 3659–3669. [CrossRef] [PubMed]
    [Google Scholar]
  36. tenOever B. R. , Sharma S. , Zou W. , Sun Q. , Grandvaux N. , Julkunen I. , Hemmi H. , Yamamoto M. , Akira S. et al. ( 2004; ). Activation of TBK1 and IKKϵ kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. . J Virol 78:, 10636–10649. [CrossRef] [PubMed]
    [Google Scholar]
  37. Vapalahti O. , Mustonen J. , Lundkvist A. , Henttonen H. , Plyusnin A. , Vaheri A. . ( 2003; ). Hantavirus infections in Europe. . Lancet Infect Dis 3:, 653–661. [CrossRef] [PubMed]
    [Google Scholar]
  38. Weber F. , Wagner V. , Rasmussen S. B. , Hartmann R. , Paludan S. R. . ( 2006; ). Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. . J Virol 80:, 5059–5064. [CrossRef] [PubMed]
    [Google Scholar]
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