Disruption of IFN-gamma- mediated antiviral activity in neurons: the role of cannabinoids.
Interferon-gamma (IFN-gamma) has potent antiviral activity in neurons which is affected by the production of nitric oxide (NO). This study examines the interactions between cannabinoid receptor-1 (CB(1)), IFNgamma-induced pathways, and inhibition of vesicular stomatitis virus (VSV) replication in neuronal cells. CB(1) is abundantly expressed in neurons of the CNS and the NB41A3 neuroblastoma cell line. CB(1) activation of NB41A3 cells by the synthetic cannabinoid, WIN55,212-2, is associated with an inhibition of Ca(2+) mobilization, leading to diminished nitric oxide synthase (NOS)-1 activity and the production of NO, in vitro. This ultimately results in antagonism of IFN-gamma-mediated antiviral activity and enhanced viral replication. Therefore, activation of cells expressing CB(1) by endogenous (or exogenous) ligands may contribute to decreased inflammation and to increased viral replication in neurons and disease in the CNS.
Department of Biology, New York University, New York, New York, USA.
R Antonio
RA
Herrera
Joseph H
JH
Oved
Carol Shoshkes
CS
Reiss
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D009474:Neurons / Q000276:immunology* / Q000821:virology; D009569:Nitric Oxide / Q000096:biosynthesis; D043882:Receptors, Cannabinoid / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000276:immunology
D002186:Cannabinoids; D007155:Immunologic Factors; D043882:Receptors, Cannabinoid; D009569:Nitric Oxide; D007371:Interferon-gamma