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Pathogenesis of HIV infection: what the virus spares is as important as what it destroys

Nature Medicine volume 12, pages 289–295 (2006)Cite this article

Abstract

Upon transmission to a new host, HIV targets CCR5+CD4+ effector memory T cells, resulting in acute, massive depletion of these cells from mucosal effector sites. This depletion does not initially compromise the regenerative capacity of the immune system because naive and most central memory T cells are spared. Here, we discuss evidence suggesting that frequent activation of these spared cells during the chronic phase of HIV infection supplies mucosal tissues with short-lived CCR5+CD4+ effector cells that prevent life-threatening infections. This immune activation also facilitates continued viral replication, but infection and killing of target T cells by HIV are selective and the impact on effector-cell lifespan is limited. We propose, however, that persistent activation progressively disrupts the functional organization of the immune system, reducing its regenerative capacity and facilitating viral evolution that leads to loss of the exquisite target cell–sparing selectivity of viral replication, ultimately resulting in AIDS.

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Figure 1: Turnover and infection of lymph node, blood and mucosal tissue CD4+ T cells at various stages of activation and differentiation are schematically shown, in the absence or presence of HIV or SIV infection.
Figure 2: Comparing the kinetics of viremia decay50 to a model of BrdU delabeling.
Figure 3: Quantitative and qualitative measures of HIV disease progression.

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Acknowledgements

This research was supported, in part, by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases. L.J.P. was supported by NIH grant AI054292.

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Authors and Affiliations

  1. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Zvi Grossman, Martin Meier-Schellersheim & William E Paul

  2. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Zvi Grossman

  3. Vaccine and Gene Therapy Institute, and Oregon Regional Primate Research Center, Oregon Health & Science University, Beaverton, 97006, Oregon, USA

    Louis J Picker

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Grossman, Z., Meier-Schellersheim, M., Paul, W. et al. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med 12, 289–295 (2006). https://doi.org/10.1038/nm1380

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