1887

Abstract

Varicella-zoster virus (VZV) is sensitive to type I and type II interferons (IFNs), which mediate antiviral effects. In this study, it was demonstrated that IFN- and IFN- inhibited the replication of VZV . Although IFN- was more effective than IFN-, the level of inhibition of VZV replication achieved by the combination of both IFNs was more than additive and it was concluded that these two cytokines acted synergistically. Expression of the IFN-induced, double-stranded RNA-activated protein kinase PKR and its phosphorylation level were not modulated strongly during ongoing replication of VZV. However, in the presence of IFN-, but not IFN-, PKR expression and its phosphorylation were increased, explaining in part the inhibition of virus replication by IFNs. The expression of herpes simplex virus Us11, a viral protein with several functions, including prevention of PKR activation, strongly increased the level of VZV replication.

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2005-01-01
2019-11-18
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References

  1. Balachandra, K., Thawaranantha, D., Ayuthaya, P. I., Bhumisawasdi, J., Shiraki, K. & Yamanishi, K. ( 1994; ). Effects of human alpha, beta and gamma interferons on varicella zoster virus in vitro. Southeast Asian J Trop Med Public Health 25, 252–257.
    [Google Scholar]
  2. Bradford, M. M. ( 1976; ). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72, 248–254.[CrossRef]
    [Google Scholar]
  3. Cassady, K. A. & Gross, M. ( 2002; ). The herpes simplex virus type 1 US11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain. J Virol 76, 2029–2035.[CrossRef]
    [Google Scholar]
  4. Cassady, K. A., Gross, M. & Roizman, B. ( 1998; ). The herpes simplex virus US11 protein effectively compensates for the γ 134.5 gene if present before activation of protein kinase R by precluding its phosphorylation and that of the α subunit of eukaryotic translation initiation factor 2. J Virol 72, 8620–8626.
    [Google Scholar]
  5. Chou, J., Chen, J.-J., Gross, M. & Roizman, B. ( 1995; ). Association of a M r 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2α and premature shutoff of protein synthesis after infection with γ 134.5 mutants of herpes simplex virus 1. Proc Natl Acad Sci U S A 92, 10516–10520.[CrossRef]
    [Google Scholar]
  6. Clemens, M. J. & Elia, A. ( 1997; ). The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 17, 503–524.[CrossRef]
    [Google Scholar]
  7. Clemens, M. J., Hershey, J. W. B., Hovanessian, A. C. & 7 other authors ( 1993; ). PKR: proposed nomenclature for the RNA-dependent protein kinase induced by interferon. J Interferon Res 13, 241.[CrossRef]
    [Google Scholar]
  8. Duc Dodon, M., Mikaélian, I., Sergeant, A. & Gazzolo, L. ( 2000; ). The herpes simplex virus 1 Us11 protein cooperates with suboptimal amounts of human immunodeficiency virus type 1 (HIV-1) Rev protein to rescue HIV-1 production. Virology 270, 43–53.[CrossRef]
    [Google Scholar]
  9. Gale, M., Jr & Katze, M. G. ( 1998; ). Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol Ther 78, 29–46.[CrossRef]
    [Google Scholar]
  10. Giraud, S., Diaz-Latoud, C., Hacot, S., Textoris, J., Bourette, R. P. & Diaz, J.-J. ( 2004; ). US11 of herpes simplex virus type 1 interacts with HIPK2 and antagonizes HIPK2-induced cell growth arrest. J Virol 78, 2984–2993.[CrossRef]
    [Google Scholar]
  11. Goodbourn, S., Didcock, L. & Randall, R. E. ( 2000; ). Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81, 2341–2364.
    [Google Scholar]
  12. He, B., Gross, M. & Roizman, B. ( 1997; ). The γ 134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A 94, 843–848.[CrossRef]
    [Google Scholar]
  13. Khoo, D., Perez, C. & Mohr, I. ( 2002; ). Characterization of RNA determinants recognized by the arginine- and proline-rich region of Us11, a herpes simplex virus type 1-encoded double-stranded RNA binding protein that prevents PKR activation. J Virol 76, 11971–11981.[CrossRef]
    [Google Scholar]
  14. Poppers, J., Mulvey, M., Khoo, D. & Mohr, I. ( 2000; ). Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein. J Virol 74, 11215–11221.[CrossRef]
    [Google Scholar]
  15. Rahaus, M. & Wolff, M. H. ( 2003; ). Reciprocal effects of Varicella-zoster virus (VZV) and AP1: activation of jun, fos and ATF-2 after VZV infection and their importance for the regulation of viral genes. Virus Res 92, 9–21.[CrossRef]
    [Google Scholar]
  16. Romano, P. R., Garcia-Barrio, M. T., Zhang, X. & 7 other authors ( 1998; ). Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2α kinases PKR and GCN2. Mol Cell Biol 18, 2282–2297.
    [Google Scholar]
  17. Sainz, B., Jr & Halford, W. P. ( 2002; ). Alpha/beta interferon and gamma interferon synergize to inhibit the replication of herpes simplex virus type 1. J Virol 76, 11541–11550.[CrossRef]
    [Google Scholar]
  18. Wong, M.-L. & Yen, Y.-R. ( 1998; ). Protein synthesis in pseudorabies virus-infected cells: decreased expression of protein kinase PKR, and effects of 2-aminopurine and adenine. Virus Res 56, 199–206.[CrossRef]
    [Google Scholar]
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