‘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

Research output: Contribution to journalReview articlepeer-review

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
Publication statusPublished - 2020 Jun

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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