TY - JOUR
T1 - Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
AU - Colonna, Lucrezia
AU - Peterson, Christopher W.
AU - Schell, John B.
AU - Carlson, Judith M.
AU - Tkachev, Victor
AU - Brown, Melanie
AU - Yu, Alison
AU - Reddy, Sowmya
AU - Obenza, Willi M.
AU - Nelson, Veronica
AU - Polacino, Patricia S.
AU - Mack, Heather
AU - Hu, Shiu Lok
AU - Zeleski, Katie
AU - Hoffman, Michelle
AU - Olvera, Joe
AU - Furlan, Scott N.
AU - Zheng, Hengqi
AU - Taraseviciute, Agne
AU - Hunt, Daniel J.
AU - Betz, Kayla
AU - Lane, Jennifer F.
AU - Vogel, Keith
AU - Hotchkiss, Charlotte E.
AU - Moats, Cassie
AU - Baldessari, Audrey
AU - Murnane, Robert D.
AU - English, Christopher
AU - Astley, Cliff A.
AU - Wangari, Solomon
AU - Agricola, Brian
AU - Ahrens, Joel
AU - Iwayama, Naoto
AU - May, Andrew
AU - Stensland, Laurence
AU - Huang, Meei Li W.
AU - Jerome, Keith R.
AU - Kiem, Hans Peter
AU - Kean, Leslie S.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.
AB - Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.
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U2 - 10.1038/s41467-018-06736-7
DO - 10.1038/s41467-018-06736-7
M3 - Article
C2 - 30361514
AN - SCOPUS:85055452335
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4438
ER -