1887

Abstract

Sin Nombre virus (SNV) and Andes virus (ANDV) cause hantavirus pulmonary syndrome (HPS) in humans. Both SNV and ANDV infect Syrian hamsters, but only ANDV causes lethal disease. A co-infection study was performed to determine which virus, SNV or ANDV, would dominate the survival outcome in hamsters. Infection of hamsters with SNV 1 day before ANDV challenge did not result in disease characteristic of the latter virus, and all animals survived challenge. Control animals infected solely with ANDV all succumbed by day 14. In contrast, when viruses were injected at the same site concurrently, all hamsters succumbed to HPS disease. Hantaviruses are segmented viruses; therefore we investigated which segment might be responsible for the protective phenotype of SNV by using two SNV/ANDV reassortant viruses, both with reciprocal M-segments from the other virus (denoted ASA and SAS). Both reassortants asymptomatically infect hamsters, similar to SNV. However, unlike SNV, 1 day prior preinfection with the reassortant virus did not prevent ANDV lethality. The ASA reassortant virus, but not SAS, protected hamsters from lethal ANDV infection when administered 3 days prior to ANDV challenge. Similar to SNV preinfection, the potent innate immune stimulator poly I:C administered to hamsters 1 day before ANDV challenge prevented lethal ANDV disease. Combined, these results suggest that the difference in pathogenicity of SNV and ANDV in hamsters involves differences in early host-pathogen interactions and resultant anti-viral immune responses of both the innate and adaptive immune system.

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2018-08-01
2019-09-23
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References

  1. French GR, Foulke RS, Brand OA, Eddy GA, Lee HW et al. Korean hemorrhagic fever: propagation of the etiologic agent in a cell line of human origin. Science 1981;211:1046–1048[PubMed]
    [Google Scholar]
  2. Nichol ST, Spiropoulou CF, Morzunov S, Rollin PE, Ksiazek TG et al. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 1993;262:914–917[PubMed]
    [Google Scholar]
  3. Schmaljohn C, Nichol ST. Bunyaviridae. In Knipe DM, Howley PM. (editors) Fields Virology Philadelphia: Lippincott, Williams, and Wilkins; 2006; pp.1741–1789
    [Google Scholar]
  4. Hammerbeck CD, Hooper JW. Hantavirus vaccines. In Levine MM. (editor) New Generation Vaccines New York: Informa healthcare; 2010; pp.905–913
    [Google Scholar]
  5. Hooper JW, Larsen T, Custer DM, Schmaljohn CS. A lethal disease model for hantavirus pulmonary syndrome. Virology 2001;289:6–14 [CrossRef][PubMed]
    [Google Scholar]
  6. Wahl-Jensen V, Chapman J, Asher L, Fisher R, Zimmerman M et al. Temporal analysis of Andes virus and Sin Nombre virus infections of Syrian hamsters. J Virol 2007;81:7449–7462 [CrossRef][PubMed]
    [Google Scholar]
  7. Safronetz D, Prescott J, Haddock E, Scott DP, Feldmann H et al. Hamster-adapted Sin Nombre virus causes disseminated infection and efficiently replicates in pulmonary endothelial cells without signs of disease. J Virol 2013;87:4778–4782 [CrossRef][PubMed]
    [Google Scholar]
  8. McElroy AK, Smith JM, Hooper JW, Schmaljohn CS. Andes virus M genome segment is not sufficient to confer the virulence associated with Andes virus in Syrian hamsters. Virology 2004;326:130–139 [CrossRef][PubMed]
    [Google Scholar]
  9. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001;413:732–738 [CrossRef][PubMed]
    [Google Scholar]
  10. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006;441:101–105 [CrossRef][PubMed]
    [Google Scholar]
  11. Cimica V, Dalrymple NA, Roth E, Nasonov A, Mackow ER. An innate immunity-regulating virulence determinant is uniquely encoded by the Andes virus nucleocapsid protein. MBio 2014;5: [CrossRef][PubMed]
    [Google Scholar]
  12. Cheng E, Wang Z, Mir MA. Interaction between hantavirus nucleocapsid protein (N) and RNA-dependent RNA polymerase (RdRp) mutants reveals the requirement of an N-RdRp interaction for viral RNA synthesis. J Virol 2014;88:8706–8712 [CrossRef][PubMed]
    [Google Scholar]
  13. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 2008;205:1601–1610 [CrossRef][PubMed]
    [Google Scholar]
  14. Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 2006;103:8459–8464 [CrossRef][PubMed]
    [Google Scholar]
  15. Gowen BB, Wong MH, Jung KH, Sanders AB, Mitchell WM et al. TLR3 is essential for the induction of protective immunity against Punta Toro virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules. J Immunol 2007;178:5200–5208[PubMed]
    [Google Scholar]
  16. Frese M, Kochs G, Feldmann H, Hertkorn C, Haller O. Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein. J Virol 1996;70:915–923[PubMed]
    [Google Scholar]
  17. Kanerva M, Mustonen J, Vaheri A. Pathogenesis of puumala and other hantavirus infections. Rev Med Virol 1998;8:67–86 [CrossRef][PubMed]
    [Google Scholar]
  18. Khaiboullina SF, Rizvanov AA, Deyde VM, St Jeor SC. Andes virus stimulates interferon-inducible MxA protein expression in endothelial cells. J Med Virol 2005;75:267–275 [CrossRef][PubMed]
    [Google Scholar]
  19. Tamura M, Asada H, Kondo K, Takahashi M, Yamanishi K. Effects of human and murine interferons against hemorrhagic fever with renal syndrome (HFRS) virus (Hantaan virus). Antiviral Res 1987;8:171–178 [CrossRef][PubMed]
    [Google Scholar]
  20. Alff PJ, Gavrilovskaya IN, Gorbunova E, Endriss K, Chong Y et al. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses. J Virol 2006;80:9676–9686 [CrossRef][PubMed]
    [Google Scholar]
  21. Brown KS, Safronetz D, Marzi A, Ebihara H, Feldmann H. Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus. J Virol 2011;85:12781–12791 [CrossRef][PubMed]
    [Google Scholar]
  22. Hooper JW, Kamrud KI, Elgh F, Custer D, Schmaljohn CS. DNA vaccination with hantavirus M segment elicits neutralizing antibodies and protects against seoul virus infection. Virology 1999;255:269–278 [CrossRef][PubMed]
    [Google Scholar]
  23. Trombley AR, Wachter L, Garrison J, Buckley-Beason VA, Jahrling J et al. Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and New World hantaviruses. Am J Trop Med Hyg 2010;82:954–960 [CrossRef][PubMed]
    [Google Scholar]
  24. Council NR Guide for the Care and Use of Laboratory Animals, 8th ed. Washington, DC: National Academies Press; 2011
    [Google Scholar]
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