TY - JOUR
T1 - ‘Rinse and Replace’
T2 - Boosting T Cell Turnover To Reduce HIV-1 Reservoirs
AU - Grossman, Zvi
AU - Singh, Nevil J.
AU - Simonetti, Francesco R.
AU - Lederman, Michael M.
AU - Douek, Daniel C.
AU - Deeks, Steven G.
AU - Kawabe, Takeshi
AU - Bocharov, Gennady
AU - Meier-Schellersheim, Martin
AU - Alon, Hagit
AU - Chomont, Nicolas
AU - Grossman, Zehava
AU - Sousa, Ana E.
AU - Margolis, Leonid
AU - Maldarelli, Frank
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - HIV-1 reservoir dynamics
KW - T cell activation bursts
KW - cell population flux
KW - functional cure
KW - polyclonal activation
UR - http://www.scopus.com/inward/record.url?scp=85084639668&partnerID=8YFLogxK
U2 - 10.1016/j.it.2020.04.003
DO - 10.1016/j.it.2020.04.003
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C2 - 32414695
AN - SCOPUS:85084639668
SN - 1471-4906
VL - 41
SP - 466
EP - 480
JO - Trends in Immunology
JF - Trends in Immunology
IS - 6
ER -