Influence of proinflammatory cytokines and chemokines on the neuropathogenesis of oncornavirus and immunosuppressive lentivirus infections.
Retroviral infection of the CNS can lead to severe debilitating neurological diseases in humans and other animals. Four general types of pathogenic effects with various retroviruses have been observed including: hemorrhage (TR1.3), spongiform encephalopathy (CasBrE, FrCasE, PVC211, NT40, Mol-ts1), demyelination with inflammatory lesions (HTLV-1, visna, CAEV), and encephalopathy with gliosis and proinflammatory chemokines and cytokines, usually with microglial giant cells and nodules [human immunodeficiencyvirus (HIV), feline immunodeficiencyvirus (FIV), simian immunodeficiency virus (SIV), Fr98]. This review focuses on this fourth group of retroviruses. In this latter group, proinflammatory cytokine and chemokine upregulation accompanies the disease process, and may influence pathogenesis by direct effects on resident CNS cells. The review first discusses the Fr98 murine polytropic virus system with particular reference to the roles of cytokines and chemokines in the pathogenic process. The Fr98 data are then compared and contrasted to the cytokine and chemokine data in the lentivirus systems, HIV, SIV, and FIV. Finally, various mechanisms are presented by which tumor necrosis factor (TNF) and several chemokines may alter the pathogenesis of retrovirus infection of the CNS.
Dept. of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. kpeterson@vetmed.lsu.edu
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D000818:Animals; D017209:Apoptosis; D020805:Central Nervous System Viral Diseases / Q000209:etiology* / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D016180:Lentivirus Infections / Q000209:etiology / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity; D008262:Macrophage Activation; D051379:Mice; D019707:Receptors, Chemokine / Q000502:physiology; D012192:Retroviridae Infections / Q000209:etiology* / Q000276:immunology; D014774:Virulence
D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine