RIG-I mediates rhabdovirus-induced inflammatory immune responses of primary human astrocytes (136.3)

Abstract

Abstract Astrocytes are ideally positioned to respond to invading pathogens of the central nervous system (CNS) and produce key inflammatory mediators following exposure to neurotropic rhabdoviruses such as rabies virus and vesicular stomatitis virus (VSV). However, the mechanisms by which resident CNS cells perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases including retinoic acid-inducible gene I (RIG-I) have been described that function as intracellular sensors of replicative RNA viruses. Here, we demonstrate that primary human astrocytes constitutively express RIG-I and show that such expression is elevated following exposure to VSV. Evidence for the functional nature of RIG-I expression in these cells comes from the observation that this molecule associates with its downstream effector molecule, interferon promoter stimulator-1, following VSV infection and from the finding that a specific ligand for RIG-I elicits astrocyte immune responses. Importantly, RIG-I knockdown significantly reduces inflammatory cytokine production by VSV-infected astrocytes and inhibits the production of soluble neurotoxic mediator(s) by these cells. These findings directly implicate RIG-I in the initiation of inflammatory immune responses by human glial cells and provide a potential mechanism underlying the inflammation and neuronal cell damage associated with acute rhabdoviral infections of the CNS.