Interferon-gamma-induced inhibition of neuronal vesicular stomatitis virus infection is STAT1 dependent.
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.
Chesler
David A
DA
Department of Biology, New York University, New York, New York 10003, USA.
Dodard
Cindy
C
Lee
Grace Y
GY
Levy
David E
DE
Reiss
Carol Shoshkes
CS
D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis / Q000187:drug effects; D010766:Phosphorylation; D018353:Rhabdoviridae Infections; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013280:Stomatitis; D015534:Trans-Activators / Q000187:drug effects* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D019950:Mitogen-Activated Protein Kinase 1