Homeostatic Proliferation Fails to Efficiently Reactivate HIV-1 Latently Infected Central Memory CD4+ T Cells

PLoS Pathogens

Alberto Bosque¹  Marylinda Famiglietti¹  Vicente Planelles²  Andrew S. Weyrich³  Claudia Goulston⁴ 

[1] Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America;Division of Infectious Diseases, Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America;International PhD School in Molecular Medicine, Basic and Applied Immunology Section, Vita-Salute San Raffaele University, Milano, Italy;Program in Human Molecular Biology and Genetics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America

关键词: Viral replication;    HIV-1;    Cell cycle;    cell division;    Homeostasis;    Memory T cells;    Viral persistence;    latency;    Flow cytometry;    T cells;   

DOI  :  10.1371/journal.ppat.1002288

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.

【 授权许可】

CC BY