Dissecting How CD4 T Cells Are Lost During HIV Infection

• Published in: Cell host & microbe 2016-03, Vol.19 (3), p.280-291
• Main Authors: Doitsh, Gilad, Greene, Warner C.
• Format: Article
• Language: English
• Subjects: CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - physiology; CD4-Positive T-Lymphocytes - virology; DNA, Viral - metabolism; HIV - pathogenicity; HIV Infections - immunology; Humans; Immune Tolerance; Pyroptosis
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2016.02.012

Although the replicative life cycle of HIV within CD4 T cells is understood in molecular detail, less is known about how this human retrovirus promotes the loss of CD4 T lymphocytes. It is this cell death process that drives clinical progression to acquired immune deficiency syndrome (AIDS). Recent studies have highlighted how abortive infection of resting and thus nonpermissive CD4 T cells in lymphoid tissues triggers a lethal innate immune response against the incomplete DNA products generated by inefficient viral reverse transcription in these cells. Sensing of these DNA fragments results in pyroptosis, a highly inflammatory form of programmed cell death, that potentially further perpetuates chronic inflammation and immune activation. As discussed here, these studies cast CD4 T cell death during HIV infection in a different light. Further, they identify drug targets that may be exploited to both block CD4 T cell demise and the chronic inflammatory response generated during pyroptosis. In this Perspective, Doitsh and Greene describe their findings on CD4 T cell death by HIV, and the role of pyroptosis as a driver of HIV pathogenesis. These findings are moving the spotlight away from the virus and toward the innate immune response launched by the host against the virus.