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

Anding Shen, Jacob J. Baker, Geoffrey L. Scott, Yelena P. Davis, Yen Yi Ho, Robert F. Siliciano

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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, includingboth 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 inthe lymphoid tissues and have frequent interactions with T cells in vivo. Our study proposes anew mechanism for infection of resting CD4+ T cells in vivo and a new mechanism for latent infection in resting CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)9768-9779
Number of pages12
JournalJournal of virology
Volume87
Issue number17
DOIs
StatePublished - 2013

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