Chapter 12 : Chemokines and the Neuropathogenesis of HIV-1 Infection

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Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) is commonly associated with a multinucleated giant cell (MNGC) encephalitis termed HIV encephalitis (HIVE). Importantly, it occurs in most, but not all, cases of dementia related to HIV-1 infection. This chapter strives to describe what is known about multinuclear phagocytes (MP) activation and neuronal dysfunction with a focus on chemokines. Mounting evidence suggests that chemokines affect the pathogenesis of HAND. First, there is a state of “immune privilege” within the central nervous system (CNS) that is, in part, an evolutionary adaptation for which increasing evidence suggests that functional immunity is quite operative in the brain. Second, the maintenance of nervous system function requires protection from a variety of environmental insults occurring during inflammatory activities, such as HIVE. Third, chemokines (chemotactic cytokines) and chemokine receptors are an important part of the immune response that affects cell migration, activation, and tissue homeostasis. Fourth, following local production, chemokines induce leukocyte cytoskeletal changes, for example, actin polymerization, optimizing cell migration to areas of microbial infection or degeneration. Chemokine receptors are critical for the infection of perivascular macrophages and microglia. It has also been shown that chemokines and their receptors play a more direct role in the neuropathogenesis of HIV-1 infection. The neuropathogenesis of HIV-1 infection revolves around inflammatory factors secreted from virus-infected and immunocompetent brain MP. Chemokines and their chemokine receptors are expressed in the nervous system, and their engagement affects neuronal and glial function.

Citation: Eggert D, Anderson E, Zheng J, Gendelman H. 2009. Chemokines and the Neuropathogenesis of HIV-1 Infection, p 151-171. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch12
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A proposed pathophysiological mechanism for how chemokines and their receptors influence the neuropathogenesis of HIV-1 infection. Transendothelial migration of monocytes into the nervous system is affected by chemokines produced by activated microglia and astrocytes. Productive HIV-1 infection is sustained in infected macrophages, although the process by which these macrophages become immunoactivated remains incompletely understood. Macrophages secrete a variety of factors, including cytokines and α and β chemokines, which affect CNS inflammation and neuronal function. Neural compromise is a consequence of intracellular signal transduction alterations induced by chemokines, HIV-1 gp120, Tat, and whole virions. Neural survival and apoptosis may be induced by chemokines.

Citation: Eggert D, Anderson E, Zheng J, Gendelman H. 2009. Chemokines and the Neuropathogenesis of HIV-1 Infection, p 151-171. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch12
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