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HIV infection of the nervous system: pathogenetic mechanisms.


3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:172. Unique

HIV-1 neuropathogenesis can be divided into three important components:1) virus entry/virus localization in the nervous system, 2) the role of viral proteins and/or cellular products in neural tissue damage, and 3)the mechanism(s) of neuronal dysfunction/damage/death. The major cell type harboring productive HIV-1 infection in the nervous system is the perivascular macrophage. It is not known if these are blood derived macrophages or resident brain microglia secondarily infected by trafficking of HIV infected T-lymphocytes. HIV-1 infection of brain astrocytes restricted to the expression of regulatory gene products has been described that may cause astrocyte dysfunction and contribute to neuronal injury or to disruption of the blood-brain barrier (BBB). Studies of the CSF and of postmortem tissues reveal a state of chronic inflammation/immune activation in the nervous system during the later stages of HIV-1 infection associated with disruption of BBB integrity. BBB damage may underlie the white matter pallor described in HIV-1 infection and could result in further entry into the nervous system of toxic viral or cellular products, or additional HIV-1 infected cells. HIV infected macrophages produce excessive amounts of pro-inflammatory cytokines, including tumor necrosis factor alpha, and platelet activating factor. These products are directly toxic to human neurons in vitro. The HIV-1 envelope glycoprotein, gp 120 may stimulate the release of toxic factors from brain macrophages. These candidate toxins of both viral and cellular origin can be antagonize by blocking NMDA (or AMPA) glutamate receptors. It has been postulated that (weak) excitotoxicity leads to oxidative stress in nerons and ultimately to apoptosis. Neuronal apoptosis has recently been described in the brains of both children and adults with HIV-1 infection.



Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.