1887

Abstract

The alphaherpesvirus simian varicella virus (SVV) causes varicella and zoster in nonhuman primates. Herpesviruses evolved elaborate mechanisms to escape host immunity, but the immune evasion strategies employed by SVV remain ill-defined. We analysed whether SVV impairs the cellular response to key antiviral cytokine interferon-γ (IFNγ). SVV infection inhibited the expression of IFNγ-induced genes like C-X-C motif chemokine 10 and interferon regulatory factor 1. Phosphorylation and nuclear translocation of the signal transducer and activator of transcription 1 (STAT1) was blocked in SVV-infected cells, which did not involve cellular and viral phosphatases. SVV infection did not downregulate IFNγ receptor α and β chain expression on the cell surface. Instead, STAT1, Janus tyrosine kinases 1 (JAK1) and JAK2 protein levels were significantly decreased in SVV-infected cells. Collectively, these results demonstrate that SVV targets three proteins in the IFNγ signal transduction pathway to escape the antiviral effects of IFNγ.

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2017-10-01
2024-12-03
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References

  1. Clarkson MJ, Thorpe E, Mccarthy K. A virus disease of captive vervet monkeys (Cercopithecus aethiops) caused by a new herpesvirus. Arch Gesamte Virusforsch 1967; 22:219–234 [View Article][PubMed]
    [Google Scholar]
  2. Gray WL. Simian varicella in Old World monkeys. Comp Med 2008; 58:22–30
    [Google Scholar]
  3. Messaoudi I, Barron A, Wellish M, Engelmann F, Legasse A et al. Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans. PLoS Pathog 2009; 5:e1000657 [View Article][PubMed]
    [Google Scholar]
  4. Mahalingam R, Smith D, Wellish M, Wolf W, Dueland AN et al. Simian varicella virus DNA in dorsal root ganglia. Proc Natl Acad Sci USA 1991; 88:2750–2752 [View Article][PubMed]
    [Google Scholar]
  5. Kolappaswamy K, Mahalingam R, Traina-Dorge V, Shipley ST, Gilden DH et al. Disseminated Simian varicella virus infection in an irradiated rhesus macaque (Macaca mulatta). J Virol 2007; 81:411–415 [View Article]
    [Google Scholar]
  6. Mahalingam R, Traina-Dorge V, Wellish M, Lorino R, Sanford R et al. Simian varicella virus reactivation in cynomolgus monkeys. Virology 2007; 368:50–59 [View Article]
    [Google Scholar]
  7. Griffin BD, Verweij MC, Wiertz EJHJ. Herpesviruses and immunity: the art of evasion. Vet Microbiol 2010; 143:89–100 [View Article]
    [Google Scholar]
  8. Vossen M, Westerhout E, Söderberg-Nauclér C, Wiertz E. Viral immune evasion: a masterpiece of evolution. Immunogenetics 2002; 54:527–542 [View Article]
    [Google Scholar]
  9. Isaacs A, Lindenmann J. Virus interference I. The interferon. Proc R Soc London Ser B, Biol Sci 1957; 147:258–267 [View Article]
    [Google Scholar]
  10. Vilcek J. Novel interferons. Nat Immunol 2003; 4:8–9 [View Article]
    [Google Scholar]
  11. Bach EA, Aguet M, Schreiber RD. The IFN γ receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 1997; 15:563–591 [View Article][PubMed]
    [Google Scholar]
  12. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-γ: an overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75:163–189 [View Article][PubMed]
    [Google Scholar]
  13. Chee AV, Roizman B. Herpes simplex virus 1 gene products occlude the interferon signaling pathway at multiple sites. J Virol 2004; 78:4185–4196 [View Article][PubMed]
    [Google Scholar]
  14. Eisemann J, Mühl-Zürbes P, Steinkasserer A, Kummer M. Infection of mature dendritic cells with herpes simplex virus type 1 interferes with the interferon signaling pathway. Immunobiology 2007; 212:877–886 [View Article]
    [Google Scholar]
  15. Liang L, Roizman B. Expression of gamma interferon-dependent genes is blocked independently by virion host shutoff RNase and by US3 protein kinase. J Virol 2008; 82:4688–4696 [View Article][PubMed]
    [Google Scholar]
  16. Miller DM, Rahill BM, Boss JM, Lairmore MD, Durbin JE et al. Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway. J Exp Med 1998; 187:675–683 [View Article][PubMed]
    [Google Scholar]
  17. Morrison TE, Mauser A, Wong A, Ting JP, Kenney SC. Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate-early protein. Immunity 2001; 15:787–799 [View Article][PubMed]
    [Google Scholar]
  18. Abendroth A, Slobedman B, Lee E, Mellins E, Wallace M et al. Modulation of major histocompatibility class II protein expression by varicella-zoster virus. J Virol 2000; 74:1900–1907 [View Article][PubMed]
    [Google Scholar]
  19. Yang E, Henriksen MA, Schaefer O, Zakharova N, Darnell JE. Dissociation time from DNA determines transcriptional function in a STAT1 linker mutant. J Biol Chem 2002; 277:13455–13462 [View Article][PubMed]
    [Google Scholar]
  20. Besser D, Bromberg JF, Darnell JE, Hanafusa H. A single amino acid substitution in the v-Eyk intracellular domain results in activation of Stat3 and enhances cellular transformation. Mol Cell Biol 1999; 19:1401–1409 [View Article][PubMed]
    [Google Scholar]
  21. Ouwendijk WJD, Abendroth A, Traina-Dorge V, Getu S, Steain M et al. T-cell infiltration correlates with cxcl10 expression in ganglia of cynomolgus macaques with reactivated simian varicella Virus. J Virol 2013; 87:2979–2982 [View Article]
    [Google Scholar]
  22. Ouwendijk WJ, Mahalingam R, de Swart RL, Haagmans BL, van Amerongen G et al. T-Cell tropism of simian varicella virus during primary infection. PLoS Pathog 2013; 9:e1003368 [View Article][PubMed]
    [Google Scholar]
  23. Gray WL, Zhou F, Noffke J, Karsten Tischer B, Tischer BK. Cloning the simian varicella virus genome in E. coli as an infectious bacterial artificial chromosome. Arch Virol 2011; 156:739–746 [View Article]
    [Google Scholar]
  24. Najarro P, Traktman P, Lewis JA. Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses stat1 activation. J Virol 2001; 75:3185–3196 [View Article]
    [Google Scholar]
  25. Baron M, Davignon JL. Inhibition of IFN-γ-induced STAT1 tyrosine phosphorylation by human CMV is mediated by SHP2. J Immunol 2008; 181:5530–5536 [View Article][PubMed]
    [Google Scholar]
  26. Rose KM, Elliott R, Martínez-Sobrido L, García-Sastre A, Weiss SR. Murine coronavirus delays expression of a subset of interferon-stimulated genes. J Virol 2010; 84:5656–5669 [View Article][PubMed]
    [Google Scholar]
  27. Verweij MC, Wellish M, Whitmer T, Malouli D, Lapel M et al. Varicella viruses inhibit interferon-stimulated JAK-STAT signaling through multiple mechanisms. PLoS Pathog 2015; 11:e1004901 [View Article]
    [Google Scholar]
  28. Whitmer T, Malouli D, Uebelhoer LS, Defilippis VR, Früh K et al. The ORF61 Protein encoded by simian varicella virus and varicella-zoster virus inhibits NF-κB signaling by interfering with IκBα degradation. J Virol 2015; 89:8687–8700 [View Article]
    [Google Scholar]
  29. Nagel MA, James SF, Traktinskiy I, Wyborny A, Choe A et al. Inhibition of phosphorylated-STAT1 nuclear translocation and antiviral protein expression in human brain vascular adventitial fibroblasts infected with varicella-zoster virus. J Virol 2014; 88:11634–11637 [View Article][PubMed]
    [Google Scholar]
  30. Oroskar AA, Read GS. Control of mRNA stability by the virion host shutoff function of herpes simplex virus. J Virol 1989; 63:1897–1906
    [Google Scholar]
  31. Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A et al. Signaling by type I and II cytokine receptors: ten years after. Curr Opin Immunol 2001; 13:363–373 [View Article]
    [Google Scholar]
  32. Haberthur K, Meyer C, Arnold N, Engelmann F, Jeske DR et al. Intrabronchial infection of rhesus macaques with simian varicella virus results in a robust immune response in the lungs. J Virol 2014; 88:12777–12792 [View Article][PubMed]
    [Google Scholar]
  33. Traina-Dorge V, Sanford R, James S, Doyle-Meyers LA, de Haro E et al. Robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques. J Neurovirol 2014; 20:526–530 [View Article]
    [Google Scholar]
  34. Nikkels AF, Sadzot-Delvaux C, Piérard GE. Absence of intercellular adhesion molecule 1 expression in varicella zoster virus–infected keratinocytes during herpes zoster. Am J Dermatopathol 2004; 26:27–32 [View Article]
    [Google Scholar]
  35. Ouwendijk WJD, Getu S, Mahalingam R, Gilden D, Osterhaus ADME et al. Characterization of the immune response in ganglia after primary simian varicella virus infection. J Neurovirol 2016; 22:376–388 [View Article]
    [Google Scholar]
  36. Ouwendijk WJD, Verjans G. Pathogenesis of varicelloviruses in primates. J Pathol 2015; 235:298–311 [View Article]
    [Google Scholar]
  37. Eisfeld AJ, Yee MB, Erazo A, Abendroth A, Kinchington PR. Downregulation of class I major histocompatibility complex surface expression by varicella-zoster virus involves open reading frame 66 protein kinase-dependent and -independent mechanisms. J Virol 2007; 81:9034–9049 [View Article][PubMed]
    [Google Scholar]
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