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J Virol. 2013 Sep;87(17):9768-79. doi: 10.1128/JVI.01478-13. Epub 2013 Jul 3.

Endothelial cell stimulation overcomes restriction and promotes productive and latent HIV-1 infection of resting CD4+ T cells.

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Department of Biology, Calvin College, Grand Rapids, Michigan, USA.


Highly active antiretroviral therapy (HAART) is able to suppress human immunodeficiency virus type 1 (HIV-1) to undetectable levels in the majority of patients, but eradication has not been achieved because latent viral reservoirs persist, particularly in resting CD4(+) T lymphocytes. It is generally understood that HIV-1 does not efficiently infect resting CD4(+) T cells, and latent infection in those cells may arise when infected CD4(+) T lymphoblasts return to resting state. In this study, we found that stimulation by endothelial cells can render resting CD4(+) T cells permissible for direct HIV infection, including both productive and latent infection. These stimulated T cells remain largely phenotypically unactivated and show a lower death rate than activated T cells, which promotes the survival of infected cells. The stimulation by endothelial cells does not involve interleukin 7 (IL-7), IL-15, CCL19, or CCL21. Endothelial cells line the lymphatic vessels in the lymphoid tissues and have frequent interactions with T cells in vivo. Our study proposes a new mechanism for infection of resting CD4(+) T cells in vivo and a new mechanism for latent infection in resting CD4(+) T cells.

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