Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

Lucrezia Colonna, Christopher W. Peterson, John B. Schell, Judith M. Carlson, Victor Tkachev, Melanie Brown, Alison Yu, Sowmya Reddy, Willi M. Obenza, Veronica Nelson, Patricia S. Polacino, Heather Mack, Shiu-Lok Hu, Katie Zeleski, Michelle Hoffman, Joe Olvera, Scott N. Furlan, Hengqi Zheng, Agne Taraseviciute, Daniel J. Hunt, Kayla Betz, Jennifer F. Lane, Keith Vogel, Charlotte E. Hotchkiss, Cassie Moats, Audrey Baldessari, Robert D. Murnane, Christopher English, Cliff A. Astley, Solomon Wangari, Brian Agricola, Joel Ahrens, Naoto Iwayama, Andrew May, Laurence Stensland, Meei-Li W. Huang, Keith R. Jerome, Hans-Peter Kiem and Leslie S. Kean ()
Additional contact information
Lucrezia Colonna: Seattle Children’s Research Institute
Christopher W. Peterson: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
John B. Schell: Seattle Children’s Research Institute
Judith M. Carlson: Seattle Children’s Research Institute
Victor Tkachev: Seattle Children’s Research Institute
Melanie Brown: Seattle Children’s Research Institute
Alison Yu: Seattle Children’s Research Institute
Sowmya Reddy: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
Willi M. Obenza: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
Veronica Nelson: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
Patricia S. Polacino: Washington National Primate Research Center
Heather Mack: Washington National Primate Research Center
Shiu-Lok Hu: Washington National Primate Research Center
Katie Zeleski: Seattle Children’s Research Institute
Michelle Hoffman: Seattle Children’s Research Institute
Joe Olvera: Washington National Primate Research Center
Scott N. Furlan: Seattle Children’s Research Institute
Hengqi Zheng: Seattle Children’s Research Institute
Agne Taraseviciute: Seattle Children’s Research Institute
Daniel J. Hunt: Seattle Children’s Research Institute
Kayla Betz: Seattle Children’s Research Institute
Jennifer F. Lane: Washington National Primate Research Center
Keith Vogel: Washington National Primate Research Center
Charlotte E. Hotchkiss: Washington National Primate Research Center
Cassie Moats: Washington National Primate Research Center
Audrey Baldessari: Washington National Primate Research Center
Robert D. Murnane: Washington National Primate Research Center
Christopher English: Washington National Primate Research Center
Cliff A. Astley: Washington National Primate Research Center
Solomon Wangari: Washington National Primate Research Center
Brian Agricola: Washington National Primate Research Center
Joel Ahrens: Washington National Primate Research Center
Naoto Iwayama: Washington National Primate Research Center
Andrew May: Washington National Primate Research Center
Laurence Stensland: University of Washington
Meei-Li W. Huang: University of Washington
Keith R. Jerome: University of Washington
Hans-Peter Kiem: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
Leslie S. Kean: Seattle Children’s Research Institute

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06736-7

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