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

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 S...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202377/
https://www.ncbi.nlm.nih.gov/pubmed/30361514
http://dx.doi.org/10.1038/s41467-018-06736-7
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author 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.
author_facet 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.
author_sort Colonna, Lucrezia
collection PubMed
description 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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spelling pubmed-62023772018-10-29 Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation 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. Nat Commun Article 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. Nature Publishing Group UK 2018-10-25 /pmc/articles/PMC6202377/ /pubmed/30361514 http://dx.doi.org/10.1038/s41467-018-06736-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title_full Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title_fullStr Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title_full_unstemmed Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title_short Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
title_sort evidence for persistence of the shiv reservoir early after mhc haploidentical hematopoietic stem cell transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202377/
https://www.ncbi.nlm.nih.gov/pubmed/30361514
http://dx.doi.org/10.1038/s41467-018-06736-7
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