Your browser doesn't support javascript.
loading
Neurotropic arboviruses induce interferon regulatory factor 3-mediated neuronal responses that are cytoprotective, interferon independent, and inhibited by Western equine encephalitis virus capsid.
Peltier, Daniel C; Lazear, Helen M; Farmer, Jocelyn R; Diamond, Michael S; Miller, David J.
Afiliación
  • Peltier DC; Departments of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
J Virol ; 87(3): 1821-33, 2013 Feb.
Article en En | MEDLINE | ID: mdl-23192868
Cell-intrinsic innate immune responses mediated by the transcription factor interferon regulatory factor 3 (IRF-3) are often vital for early pathogen control, and effective responses in neurons may be crucial to prevent the irreversible loss of these critical central nervous system cells after infection with neurotropic pathogens. To investigate this hypothesis, we used targeted molecular and genetic approaches with cultured neurons to study cell-intrinsic host defense pathways primarily using the neurotropic alphavirus western equine encephalitis virus (WEEV). We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a replication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV and the unrelated flavivirus St. Louis encephalitis virus. Furthermore, IRF-3-dependent neuronal protection from virus-mediated cytopathology occurred independently of autocrine or paracrine type I interferon activity. Despite being partially controlled by IRF-3-dependent signals, WEEV also disrupted antiviral responses by inhibiting pattern recognition receptor pathways. This antagonist activity was mapped to the WEEV capsid gene, which disrupted signal transduction downstream of IRF-3 activation and was independent of capsid-mediated inhibition of host macromolecular synthesis. Overall, these results indicate that innate immune pathways have important cytoprotective activity in neurons and contribute to limiting injury associated with infection by neurotropic arboviruses.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Arbovirus / Proteínas de la Cápside / Virus de la Encefalitis Equina del Oeste / Factor 3 Regulador del Interferón / Neuronas Límite: Animals / Humans Idioma: En Revista: J Virol Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Arbovirus / Proteínas de la Cápside / Virus de la Encefalitis Equina del Oeste / Factor 3 Regulador del Interferón / Neuronas Límite: Animals / Humans Idioma: En Revista: J Virol Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos