Primary human astrocytes functionally express RIG-I, a member of the retinoic acid-inducible gene-I family of viral pattern recognition receptors (133.48)

Abstract

Abstract Astrocytes are ideally positioned to detect and respond to invading pathogens of the CNS and previous studies have demonstrated the ability of these cells to produce key inflammatory mediators following exposure to members of the Mononegavirales order of viruses that are the causative agents of lethal human CNS diseases including rabies. However, the mechanisms by which resident cells of the CNS perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases have been described that can bind early viral replicative intermediates leading to the realization that retinoic acid-inducible gene I (RIG-I)-like helicases, such as RIG-I, function as intracellular receptors for RNA viruses. In the present study, we demonstrate that cultured primary human astrocytes constitutively express RIG-I receptor protein. Interestingly, such expression is rapidly elevated following exposure to vesicular stomatitis virus (VSV), a neurotropic rhabdovirus that closely resembles rabies virus. Evidence for the functional nature of RIG-I expression in human glial cells comes from the observation that this molecule associates with its downstream effector molecule, interferon promoter stimulator-1 (IPS-1), following VSV infection as assessed by co-immunoprecipitation techniques. Furthermore, we have confirmed that this molecule functions as an intracellular pattern recognition receptor in astrocytes by demonstrating that a putative ligand for RIG-I can elicit inflammatory cytokine production by this cell type. These findings raise the exciting possibility that RIG-I plays an important role in the detection of viral CNS pathogens and the initiation of protective immune responses or, alternatively, the progression of damaging inflammation within the brain.