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

  • Research Article
  • Published:
Virologica Sinica

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.

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Authors and Affiliations

  1. Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Oklahoma, 74078, USA

    Darla Black, Jerry Ritchey & Richard Eberle

  2. Department of Statistics, Oklahoma State University, Stillwater, OK, 74078, USA

    Mark Payton

Authors
  1. Darla Black
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  2. Jerry Ritchey
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  3. Mark Payton
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  4. Richard Eberle
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Correspondence to Richard Eberle.

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Black, D., Ritchey, J., Payton, M. et al. Role of the virion host shutoff protein in neurovirulence of monkey B virus (Macacine herpesvirus 1). Virol. Sin. 29, 274–283 (2014). https://doi.org/10.1007/s12250-014-3495-x

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  • DOI: https://doi.org/10.1007/s12250-014-3495-x

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