Neuroimmune and neurovirological aspects of human immunodeficiency virus infection.
Like most lentiviruses, HIV-1 causes both immune suppression and neurological disease. Neurological disease may occur at any stage of HIV infection but is most apparent with severe immune suppression. Cognitive impairment, reflected strikingly by HIV-associated dementia, has attracted intense interest since the outset of the HIV epidemic, and understanding of its pathogenesis has been spurred on by the emergence of several hypotheses outlining potential pathogenic mechanisms. The release of inflammatory molecules by HIV-infected microglia and macrophages and the concurrent neuronal damage play central roles in the conceptualization of HIV neuropathogenesis. Many inflammatory molecules appear to contribute to the pathogenic cascade and their individual roles remain undefined. At the same time, the abundance of virus in the brain and the type or strain of virus found in the brain may also be important codeterminants of neurological disease, as shown for other neurotropic viruses. Coreceptor use by HIV found in the brain appears to closely mirror what has been reported in systemic macrophages. The impact of HAART on viral genotype and phenotype found in the brain, and its relationship to clinical disease, remain uncertain. Several interesting animal models have been developed, using other lentiviruses, transgenic animals, and HIV-infected SCID mice, that may prove useful in future pathogenesis and therapeutic studies. Despite the progress in the understanding of HIV neuropathogenesis, many questions remain unanswered.
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Departments of Clinical Neuroscience, Microbiology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Johnson
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D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D009928:Organ Specificity; D014774:Virulence