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
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / drug effects*
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DNA-Binding Proteins / metabolism
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Interferon Regulatory Factor-1
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Interferon-gamma / pharmacology*
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Mice
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Mitogen-Activated Protein Kinase 1 / drug effects
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Mitogen-Activated Protein Kinase 1 / metabolism
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Neuroblastoma / virology
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Neurons / metabolism
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Neurons / virology*
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / metabolism
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Phosphoproteins / biosynthesis
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Phosphoproteins / drug effects
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Phosphorylation
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Rhabdoviridae Infections
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STAT1 Transcription Factor
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Signal Transduction / physiology*
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Stomatitis
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Trans-Activators / drug effects*
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Trans-Activators / metabolism
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Vesicular stomatitis Indiana virus / physiology*
Substances
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DNA-Binding Proteins
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Interferon Regulatory Factor-1
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Irf1 protein, mouse
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Phosphoproteins
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STAT1 Transcription Factor
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Stat1 protein, mouse
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Trans-Activators
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Nitric Oxide
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Interferon-gamma
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Nitric Oxide Synthase
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Mitogen-Activated Protein Kinase 1