Open AccessDisruption of IFN-γ–Mediated Antiviral Activity in Neurons: The Role of Cannabinoids
Author(s) -
Raúl Herrera,
Joseph H. Oved,
Carol Shoshkes Reiss
Publication year - 2008
Publication title -
viral immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.777
H-Index - 61
eISSN - 1557-8976
pISSN - 0882-8245
DOI - 10.1089/vim.2007.0109
Subject(s) - vesicular stomatitis virus , cannabinoid receptor , viral replication , cannabinoid , nitric oxide , interferon , biology , microbiology and biotechnology , receptor , nitric oxide synthase , antagonism , pharmacology , chemistry , virus , virology , biochemistry , endocrinology , agonist
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.