Immune responses to RNA-virus infections of the CNS

Key Points Successful clearance of virus infection from the central nervous system (CNS) requires the elimination of virus from its intracellular location without damage to essential non-renewable cells, such as neurons.Several different types of RNA virus are important causes of acute encephalomyelitis worldwide, and mechanisms of disease recovery can be studied in mouse models.Normally, the CNS is maintained in an immunologically quiescent state through interactions between neurons and microglia, and the constitutive production of immunomodulatory factors.After virus infection, innate responses are quickly activated with local expression of MHC molecules, chemokines and cytokines.The adaptive immune response is initiated outside the CNS, and circulating activated natural killer cells, T cells, B cells and macrophages enter sites of virus infection in the CNS.Immune-mediated virus clearance from neurons occurs mainly through non-cytolytic processes that are mediated by antibody specific for the virus and interferon-γ, which allow neurons to survive, although virus RNA is not completely eliminated.Immune-mediated virus clearance from glial cells is more likely to occur through cytolytic processes, but long-term control is dependent on antibody.
A successful outcome for the host of virus infection of the central nervous system (CNS) requires the elimination of the virus without damage to essential non-renewable cells, such as neurons. As a result, inflammatory responses must be tightly controlled, and many unique mechanisms seem to contribute to this control. In addition to being important causes of human disease, RNA viruses that infect the CNS provide useful models in which to study immune responses in the CNS. Recent work has shown the importance of innate immune responses in the CNS in controlling virus infection. And advances have been made in assessing the relative roles of cytotoxic T cells, antibodies and cytokines in the clearance of viruses from neurons, glial cells and meningeal cells.