Progress in clinical neurosciences: The neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy.
Despite the availability of highly active antiretroviral therapy (HAART), primary HIV-related neurological diseases remain major problems in HIV clinics. The present review examines the pathogenesis of HIV-related dementia and the less severe minor cognitive and motor deficit, together with distal sensory and drug-induced toxic polyneuropathies. Abnormal host immune responses within the nervous system and the role of viral expression and diversity are emphasized in relation to neurovirulence. Induction of innate immune responses within the central and peripheral nervous systems, largely mediated by cells of macrophage lineage, appear to be common to the development of primary HIV-related neurological disease. Activation of these cell types results in the release of a cascade of inflammatory molecules including cytokines, chemokines, matrix metalloproteinases, and arachidonic acid metabolites that influence neuronal survival. Individual viral proteins encoded by envelope and tat genes and discrete sequences within these genes influence the extent to which these pro-inflammatory molecules are induced. At the same time, systemic immune suppression may influence the occurrence and severity of HIV-related neurological diseases. Implementation of HAART and neuroprotective treatments improves neurological function although the evolution of drug-resistant viral strains limits the sustained benefits of HAART.
Power
C
C
Department of Clinical Neurosciences, University of Calgary, AB, Canada. power@ucalgary.ca
Gill
M J
MJ
Johnson
R T
RT
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000821:virology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D018696:Neuroprotective Agents