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

• Published in: Nature communications Vol. 9; no. 1; pp. 4438 - 15
• Main Authors: Colonna, Lucrezia, Peterson, Christopher W., Schell, John B., Carlson, Judith M., Tkachev, Victor, Brown, Melanie, Yu, Alison, Reddy, Sowmya, Obenza, Willi M., Nelson, Veronica, Polacino, Patricia S., Mack, Heather, Hu, Shiu-Lok, Zeleski, Katie, Hoffman, Michelle, Olvera, Joe, Furlan, Scott N., Zheng, Hengqi, Taraseviciute, Agne, Hunt, Daniel J., Betz, Kayla, Lane, Jennifer F., Vogel, Keith, Hotchkiss, Charlotte E., Moats, Cassie, Baldessari, Audrey, Murnane, Robert D., English, Christopher, Astley, Cliff A., Wangari, Solomon, Agricola, Brian, Ahrens, Joel, Iwayama, Naoto, May, Andrew, Stensland, Laurence, Huang, Meei-Li W., Jerome, Keith R., Kiem, Hans-Peter, Kean, Leslie S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/100; 13/31; 38/22; 38/77; 38/88; 38/90; 631/1647/767/1424; 631/250/1854/2812; 631/250/1904; 631/250/255/1901; Animals; Antiretroviral Therapy, Highly Active; Brain; CD8-Positive T-Lymphocytes - immunology; Chimerism; Deoxyribonucleic acid; Disease Reservoirs - virology; DNA; DNA, Viral - metabolism; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Immunity; Lymphocytes T; Macaca mulatta; Major Histocompatibility Complex; multidisciplinary; Organs; Primates; RNA, Viral - metabolism; Science; Science (multidisciplinary); Simian Acquired Immunodeficiency Syndrome - drug therapy; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - physiology; Stem cell transplantation; Stem cells; Transplantation; Transplantation, Haploidentical; Transplantation, Homologous; Transplants & implants; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06736-7

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. Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.