Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in olfactory and vomeronasal chemosensory neurons in vivo

Isamu Mori, Fumi Goshima, Daisuke Watanabe, Hiroyasu Ito, Naoki Koide, Tomoaki Yoshida, Beixing Liu, Yoshinobu Kimura, Takashi Yokochi, Yukihiro Nishiyama

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

A role for the US3 protein kinase of herpes simplex virus (HSV) in regulating virus-induced neuronal apoptosis was investigated in an experimental mouse system, in which wild-type HSV invades the central nervous system (CNS) via the olfactory and vomeronasal systems upon intranasal infection. Wild-type HSV-2 strain 186 infected a fraction of olfactory and vomeronasal chemosensory neurons without inducing apoptosis and was transmitted to the CNS, precipitating lethal encephalitis. In sharp contrast, an US3-disrupted mutant, L1BR1, induced neuronal apoptosis in these peripheral conduits upon infection, blocking viral transmission to the CNS and causing no signs of disease. An US3-repaired mutant, L1B-11, behaved similarly to the wild-type virus. Only 5 p.f.u. of L1BR1 was sufficient to compromise mice when the mutant virus was introduced directly into the olfactory bulb, a viral entry site of the CNS. These results suggest that the US3 protein kinase of HSV regulates virus-induced neuronal apoptosis in peripheral conduits and determines the neuroinvasive phenotype of HSV. Furthermore, virus-induced neuronal apoptosis of peripheral nervous system cells may be a protective host response that blocks viral transmission to the CNS.

Original languageEnglish
Pages (from-to)1806-1812
Number of pages7
JournalMicrobes and Infection
Volume8
Issue number7
DOIs
Publication statusPublished - 06-2006

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Infectious Diseases

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