Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses

• Published in: Virology (New York, N.Y.) Vol. 400; no. 2; pp. 187 - 196
• Main Authors: Chauhan, Vinita S, Furr, Samantha R, Sterka, David G, Nelson, Daniel A, Moerdyk-Schauwecker, Megan, Marriott, Ian, Grdzelishvili, Valery Z
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.05.2010
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMALS; Astrocytes; Astrocytes - virology; Cells, Cultured; CENTRAL NERVOUS SYSTEM; Cytokines - metabolism; DISEASES; ENCEPHALITIS; Encephalitis, Viral - pathology; Encephalitis, Viral - virology; Infectious Disease; INFLAMMATION; MAMMALS; MEMBRANE PROTEINS; MICE; Mice, Inbred C57BL; Microglia; MICROORGANISMS; NERVOUS SYSTEM; NERVOUS SYSTEM DISEASES; Neuroglia - virology; NUCLEIC ACIDS; ORGANIC COMPOUNDS; Paramyxovirus; PARASITES; PATHOLOGICAL CHANGES; PATTERN RECOGNITION; PROLIFERATION; PROTEINS; RECEPTORS; Rhabdoviridae Infections - pathology; Rhabdoviridae Infections - virology; Rhabdoviruses; RNA; RODENTS; Sendai virus; SYMPTOMS; VERTEBRATES; Vesicular stomatitis virus; Vesiculovirus - growth & development; Vesiculovirus - immunology; Vesiculovirus - pathogenicity; VIRUSES; Vesicular stomatitis virus; Encephalitis; Sendai virus; Astrocytes; Rhabdoviruses; Paramyxovirus; Microglia
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2010.01.025

Abstract Vesicular stomatitis virus (VSV) infection of mice via intranasal administration results in a severe encephalitis with rapid activation and proliferation of microglia and astrocytes. We have recently shown that these glial cells express RIG-I and MDA5, cytosolic pattern recognition receptors for viral RNA. However, it is unclear whether VSV can replicate in glial cells or if such replication is required for their inflammatory responses. Here we demonstrate that primary microglia and astrocytes are permissive for VSV infection and limited productive replication. Importantly, we show that viral replication is required for robust inflammatory mediator production by these cells. Finally, we have confirmed that in vivo VSV administration can result in viral infection of glial cells in situ. These results suggest that viral replication within resident glial cells might play an important role in CNS inflammation following infection with VSV and possibly other neurotropic nonsegmented negative-strand RNA viruses.