Virologica Sinica

, Volume 29, Issue 5, pp 274–283 | Cite as

Role of the virion host shutoff protein in neurovirulence of monkey B virus (Macacine herpesvirus 1)

  • Darla Black
  • Jerry Ritchey
  • Mark Payton
  • Richard Eberle
Research Article

Abstract

Monkey B virus (Macacine herpesvirus 1; BV) is noted for its extreme neurovirulence in humans. Since the vhs protein encoded by the UL41 gene has been shown to be a neurovirulence factor in the related human herpes simplex viruses, the role of the UL41 gene in BV neurovirulence was investigated. BV mutants were constructed that lacked the entire UL41 ORF (Δ41) or had the RNase active site mutated (Δ41A). Neither mutant shut off host protein synthesis, degraded β-actin mRNA, or prevented an IFN-β response, indicating that the vhs protein and its RNase activity are both necessary for these activities. Replication of both mutants in primary mouse cells was impaired and they exhibited a prolonged disease course in mice. Whereas Δ41 infected mice were euthanized for symptoms related to central nervous system (CNS) infection, Δ41A infected mice were euthanized primarily for symptoms of autonomic nervous system dysfunction. While neuroinvasiveness was not affected, lesions in the CNS were more limited in size, anatomical distribution, and severity than for wild-type virus. These results indicate that the vhs protein affects the general replicative efficiency of BV in vivo rather than being a specific neurovirulence factor critical for invasion of or preferential replication in the CNS.

Keywords

herpesvirus monkey B virus UL41 virion host shutoff neurovirulence 

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References

  1. Barzilai A, Zivony-Elbom I, Sarid R, Noah E, Frenkel N, 2006. The herpes simplex virus type 1 vhs-UL41 gene secures viral replication by temporarily evading apoptotic cellular response to infection: Vhs-UL41 activity might require interactions with elements of cellular mRNA degradation machinery. J Virol, 80: 505–513.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Black D H, Saliki J T, Eberle R. 2002. Development of a green fluorescent protein reporter cell line to reduce biohazards associated with detection of infectious Cercopithecine herpesvirus 1 (monkey B virus) in clinical specimens. Compar Med, 52:534–542.Google Scholar
  3. Chou J, Kern E R, Whitley R J, Roizman B. 1990. Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science, 250: 1262–1266.PubMedCrossRefGoogle Scholar
  4. Dauber B, Pelletier J, Smiley J R. 2011. The herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner. J Virol, 85:5363–5373.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Duerst R J, Morrison L A. 2004. Herpes simplex virus 2 virion host shutoff protein interferes with type I interferon production and responsiveness. Virology, 322:158–167.PubMedCrossRefGoogle Scholar
  6. Elmore D, Eberle R. 2008. Monkey B virus (Cercopithecine herpesvirus 1). Compar Med, 58:11–21.Google Scholar
  7. Esclatine A, Taddeo B, Evans L, Roizman B. 2004a. The herpes simplex virus 1 UL41 gene-dependent destabilization of cellular RNAs is selective and may be sequence-specific. Proc Natl Acad Sci U S A, 101:3603–3608.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Esclatine A, Taddeo B, Roizman B. 2004b. The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs. Proc Natl Acad Sci U S A, 101:18165–18170.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Everly D N, Feng P, Mian I S, Read G S. 2002. mRNA degradation by the virion host shutoff (vhs) protein of herpes simplex virus: genetic and biochemical evidence that vhs is a nuclease. J Virol, 76:8560–8571.PubMedCrossRefGoogle Scholar
  10. Feng P, Everly D N, Jr., Read G S. 2005. mRNA decay during herpes simplex virus (HSV) infections: protein-protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A. J Virol, 79, 9651–9664.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Hilliard J K, Eberle R, Lipper S L, Munoz R M, Weiss S A. 1987. Herpesvirus simiae (B virus): replication of the virus and identification of viral polypeptides in infected cells. Arch Virol, 93:185–198.PubMedCrossRefGoogle Scholar
  12. Huff J L, Barry P A. 2003. B-virus (Cercopithecine herpesvirus 1) infection in humans and macaques: potential for zoonotic disease. Emer Infect Dis, 9, 246–250.CrossRefGoogle Scholar
  13. Hull R N, 1971. B virus vaccine. Lab Anim Sci, 21:1068–1071.PubMedGoogle Scholar
  14. Jing X, Cerveny M, Yang K, He B. 2004. Replication of herpes simplex virus 1 depends on the gamma 134.5 functions that facilitate virus response to interferon and egress in the different stages of productive infection. J Virol, 78:7653–7666.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Karr B M, Read G S. 1999. The virion host shutoff function of herpes simplex virus degrades the 5′ end of a target mRNA before the 3′ end. Virology, 264:195–204.PubMedCrossRefGoogle Scholar
  16. Korom M, Wylie K M, Morrison L A. 2008. Selective ablation of virion host shutoff protein RNase activity attenuates herpes simplex virus 2 in mice. J Virol, 82:3642–3653.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Lundberg P, Ramakrishna C, Brown J, Tyszka J M, Hamamura M, Hinton D R, Kovats S, Nalcioglu O, Weinberg K, Openshaw H, Cantin E M. 2008. The immune response to herpes simplex virus type 1 infection in susceptible mice is a major cause of central nervous system pathology resulting in fatal encephalitis. J Virol, 82:7078–7088.PubMedCrossRefPubMedCentralGoogle Scholar
  18. MacLean A R, ul-Fareed M, Robertson L, Harland J, Brown S M. 1991. Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. J Gen Virol, 72(Pt 3):631–639.PubMedCrossRefGoogle Scholar
  19. Mossman K L, Ashkar A A. 2005. Herpesviruses and the innate immune response. Viral Immunol, 18: 267–281.PubMedCrossRefGoogle Scholar
  20. Ohsawa K, Black D, Ohsawa M, Eberle R. 2014. Genome sequence of a pathogenic isolate of monkey B virus (species Macacine herpesvirus 1). Arch Virol, 159(10):2819–2821.PubMedCrossRefGoogle Scholar
  21. Page H G, Read G S. 2010. The virion host shutoff endonuclease (UL41) of herpes simplex virus interacts with the cellular capbinding complex eIF4F. J Virol, 84:6886–6890.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Pasieka T J, Lu B, Crosby S D, Wylie K M, Morrison L A, Alexander D E, Menachery V D, Leib D A. 2008. Herpes simplex virus virion host shutoff attenuates establishment of the antiviral state. J Virol, 82:5527–5535.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Paul S, Ricour C, Sommereyns C, Sorgeloos F, Michiels T. 2007. Type I interferon response in the central nervous system. Biochimie, 89:770–778.PubMedCrossRefGoogle Scholar
  24. Perelygina L, Zhu L, Zurkuhlen H, Mills R, Borodovsky M, Hilliard J K. 2003. Complete sequence and comparative analysis of the genome of herpes B virus (Cercopithecine herpesvirus 1) from a rhesus monkey. J Virol, 77:6167–6177.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Ritchey J W, Ealey K A, Payton M, Eberle R. 2002. Comparative pathology of infections with baboon and African green monkey alpha-herpesviruses in mice. J Compar Pathol, 127:150–161.CrossRefGoogle Scholar
  26. Rogers K M, Black D H, Eberle R. 2007. Primary mouse dermal fibroblast cell cultures as an in vitro model system for the differential pathogenicity of cross-species herpesvirus papio 2 infections. Arch Virol, 152: 543–552.PubMedCrossRefGoogle Scholar
  27. Rogers K M, Deatheridge M, Breshears M A, Chapman S, Black D, Ritchey J W, Payton M, Eberle R. 2009. Type I IFN response to Papiine herpesvirus 2 (Herpesvirus papio 2; HVP2) determines neuropathogenicity in mice. Virology, 386:280–289.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Rogers K M, Ritchey J W, Payton M, Black D H, Eberle R. 2006. Neuropathogenesis of Herpesvirus papio 2 in Mice Parallels Cercopithecine herpesvirus 1 (B Virus) Infections in Humans. J Gen Virol, 87:267–276.PubMedCrossRefGoogle Scholar
  29. Saffran H A, Read G S, Smiley J R. 2010. Evidence for translational regulation by the herpes simplex virus virion host shutoff protein. J Virol, 84:6041–6049.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Shu M, Taddeo B, Zhang W, Roizman B. 2013. Selective degradation of mRNAs by the HSV host shutoff RNase is regulated by the UL47 tegument protein. Proc Natl Acad Sci U S A, 110: E1669–E1675.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Simon M A, Daniel M D, Lee-Parritz D, King N W, Ringler D J. 1993. Disseminated B virus infection in a cynomolgus monkey. Lab Anim Sci, 43:545–550.PubMedGoogle Scholar
  32. Smibert C A, Popova B, Xiao P, Capone J P, Smiley J R. 1994. Herpes simplex virus VP16 forms a complex with the virion host shutoff protein vhs. J Virol, 68:2339–2346.PubMedPubMedCentralGoogle Scholar
  33. Smiley J R, Elgadi M M, Saffran H A. 2001. Herpes simplex virus vhs protein. Meth Enzymol, 342:440–451.PubMedCrossRefGoogle Scholar
  34. Smith T J, Morrison L A, Leib D A. 2002. Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants. J Virol, 76:2054–2061.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Strelow L I, Leib D A. 1995. Role of the viron host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. J Virol, 69:6779–6786.PubMedPubMedCentralGoogle Scholar
  36. Suzutani T, Nagamine M, Shibaki T, Ogasawara M, Yoshida I, Daikoku T, Nishiyama Y, Azuma M. 2000. The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection. J Gen Virol, 81:1763–1771.PubMedGoogle Scholar
  37. Taddeo B, Sciortino M T, Zhang W, Roizman B. 2007. Interaction of herpes simplex virus RNase with VP16 and VP22 is required for the accumulation of the protein but not for accumulation of mRNA. Proc Natl Acad Sci U S A, 104:12163–12168.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Taddeo B, Zhang W, Roizman B. 2006. The U(L)41 protein of herpes simplex virus 1 degrades RNA by endonucleolytic cleavage in absence of other cellular or viral proteins. Proc Natl Acad Sci U S A, 103: 2827–2832.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Taddeo B, Zhang W, Roizman B. 2013. The herpes simplex virus host shutoff RNase degrades cellular and viral mRNAs made before infection but not viral mRNA made after infection. J Virol, 87:4516–4522.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Takeuchi O, Akira S. 2007. Recognition of viruses by innate immunity. Immunol Rev, 220:214–224.PubMedCrossRefGoogle Scholar
  41. Zelus B D, Stewart R S, Ross J. 1996. The virion host shutoff protein of herpes simplex virus type 1: messenger ribonucleolytic activity in vitro. J Virol, 70:2411–2419.PubMedPubMedCentralGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Darla Black
    • 1
  • Jerry Ritchey
    • 1
  • Mark Payton
    • 2
  • Richard Eberle
    • 1
  1. 1.Department of Veterinary Pathobiology, Center for Veterinary Health SciencesOklahoma State UniversityOklahomaUSA
  2. 2.Department of StatisticsOklahoma State UniversityStillwaterUSA

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