Directly Infected Resting CD4+T Cells Can Produce HIV Gag without Spreading Infection in a Model of HIV Latency

PLoS Pathogens

Frances Male¹  Troy Brady¹  Frederic D. Bushman¹  Erin H. Graf²  Matthew J. Pace²  Luis M. Agosto²  Una O'Doherty²  Angela M. Mexas² 

[1]Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America

[2]Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America

关键词: HIV;    HIV infections;    Protein expression;    Highly-active antiretroviral therapy;    Protease inhibitors;    Cytokines;    Cell staining;    Site selection;   

DOI  :  10.1371/journal.ppat.1002818

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response.

【 授权许可】

CC BY