Interferon-gamma-induced inhibition of neuronal vesicular stomatitis virus infection is STAT1 dependent

J Neurovirol. 2004 Feb;10(1):57-63. doi: 10.1080/13550280490261707.

Abstract

In this report, the signaling pathways utilized by interferon (IFN)-gamma in neurons and their respective roles in the inhibition of vesicular stomatitis virus (VSV) replication were studied. The authors have previously shown that IFN-gamma treatment of NB41A3 neuroblastoma cells results in a 2-log inhibition of VSV production. This inhibition of VSV replication is dependent both in vitro and in vivo on nitric oxide (NO) production by NO synthase (NOS)-1. In NB41A3 neuroblastoma cells, IFN-gamma was found to induce the signal transducer and activator of transcription (STAT) STAT1 phosphorylation, interferon regulatory factor (IRF)-1 expression, and p42/p44 mitogen-activated protein kinase (MAPK) phosphorylation; MAPK, however, was not required for inhibition of viral replication. Using olfactory bulb-enriched primary neuronal cultures, the inhibition of VSV replication was found to be STAT1 dependent, but did not require IRF-1.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / metabolism
  • Interferon Regulatory Factor-1
  • Interferon-gamma / pharmacology*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Neuroblastoma / virology
  • Neurons / metabolism
  • Neurons / virology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / drug effects
  • Phosphorylation
  • Rhabdoviridae Infections
  • STAT1 Transcription Factor
  • Signal Transduction / physiology*
  • Stomatitis
  • Trans-Activators / drug effects*
  • Trans-Activators / metabolism
  • Vesicular stomatitis Indiana virus / physiology*

Substances

  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Trans-Activators
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Mitogen-Activated Protein Kinase 1