Innate immunity in the pathogenesis of polytropic retrovirus infection in the central nervous system.
Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease.
Peterson
Karin E
KE
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South 4th Street, Hamilton, MT 59840, USA. petersonka@niaid.nih.gov
Du
Min
M
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002494:Central Nervous System Infections / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D012190:Retroviridae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7