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. HuntKayla 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, Leslie S. Kean

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Article number4438
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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