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Progress in Clinical Neurosciences: The Neuropathogenesis of HIV Infection: Host-Virus Interaction and the Impact of Therapy

  • C. Power (a1), M.J. Gill (a2) and R.T. Johnson (a3)

Abstract

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.

RÉSUMÉ:

Malgré la disponibilité de la thérapie antirétrovirale hautement efficace (HAART), les maladies neurologiques reliées à l'infection par le VIH demeurent un problème majeur dans les cliniques de traitement de l'infection par le VIH. Cette revue examine la pathogenèse de la démence reliée au VIH et des déficits cognitifs et moteurs de moindre importance, ainsi que les polyneuropathies sensitives distales, induites par la toxicité des médicaments. Les réponses immunitaires anormales de l'hôte dans le système nerveux et le rôle de l'expression et de la diversité virale sont soulignés en relation avec la neurovirulence. L'induction des réponses immunitaires innées dans le système nerveux central et périphérique, en grande partie médiée par les cellules de la lignée macrophagique, semble être commune au développement des maladies neurologiques reliées au VIH. L'activation de ces types de cellules provoque la libération d'une cascade de molécules inflammatoires incluant des cytokines, des chemokines, des métalloprotéinases de la matrice et des métabolites de l'acide arachidonique qui influencent la survie neuronale. Des protéines virales individuelles codées par des gènes de l'enveloppe et des gènes tat, ainsi que des séquences discrètes dans ces gènes, influencent le niveau d'induction de ces molécules pro-inflammatoires. De plus, la suppression immunitaire systémique peut influencer l'apparition et la sévérité de maladies neurologiques reliées au VIH. Le traitement HAART et les traitements neuroprotecteurs améliorent la fonction neurologique, bien que l'évolution de souches virales résistantes à la médication limite les bénéfices à long terme du traitement HAART.

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Progress in Clinical Neurosciences: The Neuropathogenesis of HIV Infection: Host-Virus Interaction and the Impact of Therapy

  • C. Power (a1), M.J. Gill (a2) and R.T. Johnson (a3)

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