‘Rinse and Replace’: Boosting T Cell Turnover To Reduce HIV-1 Reservoirs

Zvi Grossman*, Nevil J. Singh, Francesco R. Simonetti, Michael M. Lederman, Daniel C. Douek, Steven G. Deeks, Takeshi Kawabe, Gennady Bocharov, Martin Meier-Schellersheim, Hagit Alon, Nicolas Chomont, Zehava Grossman, Ana E. Sousa, Leonid Margolis, Frank Maldarelli

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

Abstract

Latent HIV-1 persists indefinitely during antiretroviral therapy (ART) as an integrated silent genome in long-lived memory CD4+ T cells. In untreated infections, immune activation increases the turnover of intrinsically long-lived provirus-containing CD4+ T cells. Those are ‘washed out’ as a result of their activation, which when coupled to viral protein expression can facilitate local inflammation and recruitment of uninfected cells to activation sites, causing latently infected cells to compete for survival. De novo infection can counter this washout. During ART, inflammation and CD4+ T cell activation wane, resulting in reduced cell turnover and a persistent reservoir. We propose accelerating reservoir washout during ART by triggering sequential waves of polyclonal CD4+ T cell activation while simultaneously enhancing virus protein expression. Reservoir reduction as an adjunct to other therapies might achieve lifelong viral control.

Original languageEnglish
Pages (from-to)466-480
Number of pages15
JournalTrends in Immunology
Volume41
Issue number6
DOIs
StatePublished - Jun 2020

Funding

FundersFunder number
BryoLogyx
Enochian Biosciences
amfAR Institute for HIV-1 Cure ResearchamfAR 109301
National Institute of Allergy and Infectious DiseasesR01AI110719
Merck
Gilead Sciences
Delaney AIDS Research EnterpriseA127966
Russian Science Foundation18-11-00171

    Keywords

    • HIV-1 reservoir dynamics
    • T cell activation bursts
    • cell population flux
    • functional cure
    • polyclonal activation

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