HIV preferentially infects HIV-specific CD4+ T cells

Abstract

HIV infection is associated with the progressive loss of CD4+ T cells through their destruction or decreased production1,2. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4+ T cells are preferentially affected3,4,5. Here we show that HIV-specific memory CD4+ T cells in infected individuals contain more HIV viral DNA than other memory CD4+ T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4+ T cells increases to a greater extent than in memory CD4+ T cells of other specificities. These findings show that HIV-specific CD4+ T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4+ T-cell responses, and consequently the loss of immunological control of HIV replication6. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.

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Figure 1: HIV viral DNA content of memory CD4+ T cells in infected individuals.
Figure 2: Effects of cell division and interferon-γ secretion on HIV infection of CD4+ T cells that had been stimulated by staphylococcal enterotoxin B.
Figure 3: Viral DNA content of memory CD4+ T cells in infected individuals on and off antiretroviral therapy, ART.

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Acknowledgements

We thank the patients and staff at UTSW Medical Center and the NIH for their cooperation, and M. Roederer and J. Mascola for their help. This work was supported by the UK Medical Research Council (D.A.P.), the Wellcome Trust, and the National Institutes of Health (S.W.).

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Correspondence to Daniel C. Douek.

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Douek, D., Brenchley, J., Betts, M. et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417, 95–98 (2002) doi:10.1038/417095a

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