Disruption of IFN-γ-Mediated Antiviral Activity in Neurons: The Role of Cannabinoids

R Herrera

Joseph Oved

Carol Reiss

^{Department of Biology, Center for Neural Science, New York University, New York, New York.}

^{Center for Neural Science, New York University, New York, New York.}

^{Department of Microbiology and NYU Cancer Center, New York University School of Medicine, New York, New York.}

^{Department of Microbiology, Mount Sinai School of Medicine, New York, New York.}

^{Corresponding author.}

Address reprint requests to: Dr. Carol Shoshkes Reiss, Department of Biology, New York University, 100 Washington Sq. East, Mail Code 5181, New York, New York 10003-6688. E-mail:ude.uyn@ssier.lorac

^{R.A. Herrera and J.H. Oved contributed equally to this project.}

Address reprint requests to: Dr. Carol Shoshkes Reiss, Department of Biology, New York University, 100 Washington Sq. East, Mail Code 5181, New York, New York 10003-6688. E-mail:ude.uyn@ssier.lorac

Received 2007 Dec 21; Accepted 2008 Feb 18.

Abstract

Interferon-γ (IFN-γ) 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), IFNγ–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 Ca^{mobilization, leading to diminished nitric oxide synthase (NOS)-1 activity and the production of NO,}in vitro. This ultimately results in antagonism of IFN-γ–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.

Abstract

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