TY - JOUR
T1 - Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques
AU - Wu, Helen L.
AU - Busman-Sahay, Kathleen
AU - Weber, Whitney C.
AU - Waytashek, Courtney M.
AU - Boyle, Carla D.
AU - Bateman, Katherine B.
AU - Reed, Jason S.
AU - Hwang, Joseph M.
AU - Shriver-Munsch, Christine
AU - Swanson, Tonya
AU - Northrup, Mina
AU - Armantrout, Kimberly
AU - Price, Heidi
AU - Robertson-LeVay, Mitch
AU - Uttke, Samantha
AU - Kumar, Mithra R.
AU - Fray, Emily J.
AU - Taylor-Brill, Sol
AU - Bondoc, Stephen
AU - Agnor, Rebecca
AU - Junell, Stephanie L.
AU - Legasse, Alfred W.
AU - Moats, Cassandra
AU - Bochart, Rachele M.
AU - Sciurba, Joseph
AU - Bimber, Benjamin N.
AU - Sullivan, Michelle N.
AU - Dozier, Brandy
AU - MacAllister, Rhonda P.
AU - Hobbs, Theodore R.
AU - Martin, Lauren D.
AU - Panoskaltsis-Mortari, Angela
AU - Colgin, Lois M.A.
AU - Siliciano, Robert F.
AU - Siliciano, Janet D.
AU - Estes, Jacob D.
AU - Smedley, Jeremy V.
AU - Axthelm, Michael K.
AU - Meyers, Gabrielle
AU - Maziarz, Richard T.
AU - Burwitz, Benjamin J.
AU - Stanton, Jeffrey J.
AU - Sacha, Jonah B.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/7/11
Y1 - 2023/7/11
N2 - Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
AB - Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
KW - CCR5
KW - GVHD
KW - HIV
KW - HSCT
KW - SIV
UR - https://www.scopus.com/pages/publications/85163166868
UR - https://www.scopus.com/pages/publications/85163166868#tab=citedBy
U2 - 10.1016/j.immuni.2023.04.019
DO - 10.1016/j.immuni.2023.04.019
M3 - Article
C2 - 37236188
AN - SCOPUS:85163166868
SN - 1074-7613
VL - 56
SP - 1649-1663.e5
JO - Immunity
JF - Immunity
IS - 7
ER -
SDG 3 Good Health and Well-being