Corneal replication is an interferon response-independent bottleneck for virulence of herpes simplex virus 1 in the absence of virion host shutoff

J Virol. 2012 Jul;86(14):7692-5. doi: 10.1128/JVI.00761-12. Epub 2012 May 2.

Abstract

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR(-/-)) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / virology
  • Cornea / pathology
  • Cornea / virology*
  • Dendritic Cells / virology
  • Herpesvirus 1, Human / pathogenicity*
  • Herpesvirus 1, Human / physiology
  • Interferon Type I / immunology*
  • Interferon-gamma / immunology*
  • Keratitis, Herpetic / virology*
  • Mice
  • Mice, Transgenic
  • Ribonucleases / genetics
  • Ribonucleases / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Replication

Substances

  • Interferon Type I
  • Viral Proteins
  • virion host shutoff protein, Simplexvirus
  • Interferon-gamma
  • Ribonucleases