Disruption of IFN-gamma-mediated antiviral activity in neurons: The role of cannabinoids

作者：Herrera R Antonio; Oved Joseph H; Reiss Carol Shoshkes^*

来源：Viral Immunology, 2008, 21(2): 141-152.

DOI：10.1089/vim.2007.0109

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 (CB1), IFN gamma-induced pathways, and inhibition of vesicular stomatitis virus (VSV) replication in neuronal cells. CB1 is abundantly expressed in neurons of the CNS and the NB41A3 neuroblastoma cell line. CB1 activation of NB41A3 cells by the synthetic cannabinoid, WIN55,212-2, is associated with an inhibition of Ca2+ 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 CB1 by endogenous (or exogenous) ligands may contribute to decreased inflammation and to increased viral replication in neurons and disease in the CNS.

• 出版日期2008-6