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

Anding Shen, Calvin University
Jacob J. Baker, Calvin University
Geoffrey L. Scott, Calvin University
Yelena P. Davis, Calvin University


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. © 2013, American Society for Microbiology.