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The Role of Monocytes and Macrophages in the Pathogenesis of HIV-1 Infection

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Cells of the macrophage lineage play an important role in initial infection with HIV-1 and contribute to the pathogenesis of the disease throughout the course of infection. Both blood monocytes and tissue macrophages can be infected with HIV-1 in vivo and in vitro, although the latter are more susceptible to infection. They express the CD4 receptor and chemokine coreceptors for HIV-1 entry, and hence are targets for HIV-1 infection. Cells of the macrophage lineage can be infected predominantly with macrophage (M)-tropic strains, although infection with some T cell line (T)-tropic strains or dual-tropic isolates of HIV-1 (exhibiting features of both M-tropic and T-tropic isolates) has also been reported. Following infection with HIV-1, monocyte / macrophages are resistant to cytopathic effects and persist throughout the course of infection as long-term stable reservoirs for HIV-1 capable of disseminating the virus to tissues. Infectious virus can be recovered from blood monocytes obtained from patients receiving highly active antiretroviral therapy with no detectable HIV-1 in blood. Cells of the macrophage lineage play an important role in the neuropathogenesis of HIV-1 infection and contribute to HIV-induced dementia via production of proinflammatory cytokines and neurotoxins. Following HIV-1 infection, effector functions carried out by monocyte / macrophages are also impaired, including phagocytosis, intracellular killing, chemotaxis and cytokine production. Such defects contribute to the pathogenesis of AIDS by allowing reactivation and development of opportunistic infections. This review focuses on the overall role of monocytes and macrophages in the pathogenesis of HIV-1 infection and considers the mechanisms underlying defective monocyte / macrophage function.
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Keywords: hiv; macrophage function; monocytes/macrophages; neuropathogenesis; phagocytosis; viral reservoirs

Document Type: Review Article

Publication date: 01 November 2002

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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