Cargando…

The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection

Despite advances in hematopoietic stem/progenitor cell (HSPC) transplant for HIV-1–infected patients, the impact of a preexisting HIV-1 infection on the engraftment and clonal repopulation of HSPCs remains poorly understood. We have developed a long terminal repeat indexing-mediated integration site...

Descripción completa

Detalles Bibliográficos
Autores principales: Suryawanshi, Gajendra W., Khamaikawin, Wannisa, Wen, Jing, Shimizu, Saki, Arokium, Hubert, Xie, Yiming, Wang, Eugene, Kim, Shihyoung, Choi, Hyewon, Zhang, Chong, Yu, Hannah, Presson, Angela P., Kim, Namshin, An, Dong-Sung, Chen, Irvin S. Y., Kim, Sanggu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385479/
https://www.ncbi.nlm.nih.gov/pubmed/32766447
http://dx.doi.org/10.1126/sciadv.aay9206
_version_ 1783563794142724096
author Suryawanshi, Gajendra W.
Khamaikawin, Wannisa
Wen, Jing
Shimizu, Saki
Arokium, Hubert
Xie, Yiming
Wang, Eugene
Kim, Shihyoung
Choi, Hyewon
Zhang, Chong
Yu, Hannah
Presson, Angela P.
Kim, Namshin
An, Dong-Sung
Chen, Irvin S. Y.
Kim, Sanggu
author_facet Suryawanshi, Gajendra W.
Khamaikawin, Wannisa
Wen, Jing
Shimizu, Saki
Arokium, Hubert
Xie, Yiming
Wang, Eugene
Kim, Shihyoung
Choi, Hyewon
Zhang, Chong
Yu, Hannah
Presson, Angela P.
Kim, Namshin
An, Dong-Sung
Chen, Irvin S. Y.
Kim, Sanggu
author_sort Suryawanshi, Gajendra W.
collection PubMed
description Despite advances in hematopoietic stem/progenitor cell (HSPC) transplant for HIV-1–infected patients, the impact of a preexisting HIV-1 infection on the engraftment and clonal repopulation of HSPCs remains poorly understood. We have developed a long terminal repeat indexing-mediated integration site sequencing (LTRi-Seq) method that provides a multiplexed clonal quantitation of both anti–HIV-1 RNAi (RNA interference) gene-modified and control vector-modified cell populations, together with HIV-1–infected cells—all within the same animal. In our HIV-1–preinfected humanized mice, both therapeutic and control HSPCs repopulated efficiently without abnormalities. Although the HIV-1–mediated selection of anti–HIV-1 RNAi-modified clones was evident in HIV-1–infected mice, the organ-to-organ and intra-organ clonal distributions in infected mice were indistinguishable from those in uninfected mice. HIV-1–infected cells showed clonal patterns distinct from those of HSPCs. Our data demonstrate that, despite the substantial impact of HIV-1 infection on CD4(+) T cells, HSPC repopulation remains polyclonal, thus supporting the use of HSPC transplant for anti-HIV treatment.
format Online
Article
Text
id pubmed-7385479
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-73854792020-08-05 The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection Suryawanshi, Gajendra W. Khamaikawin, Wannisa Wen, Jing Shimizu, Saki Arokium, Hubert Xie, Yiming Wang, Eugene Kim, Shihyoung Choi, Hyewon Zhang, Chong Yu, Hannah Presson, Angela P. Kim, Namshin An, Dong-Sung Chen, Irvin S. Y. Kim, Sanggu Sci Adv Research Articles Despite advances in hematopoietic stem/progenitor cell (HSPC) transplant for HIV-1–infected patients, the impact of a preexisting HIV-1 infection on the engraftment and clonal repopulation of HSPCs remains poorly understood. We have developed a long terminal repeat indexing-mediated integration site sequencing (LTRi-Seq) method that provides a multiplexed clonal quantitation of both anti–HIV-1 RNAi (RNA interference) gene-modified and control vector-modified cell populations, together with HIV-1–infected cells—all within the same animal. In our HIV-1–preinfected humanized mice, both therapeutic and control HSPCs repopulated efficiently without abnormalities. Although the HIV-1–mediated selection of anti–HIV-1 RNAi-modified clones was evident in HIV-1–infected mice, the organ-to-organ and intra-organ clonal distributions in infected mice were indistinguishable from those in uninfected mice. HIV-1–infected cells showed clonal patterns distinct from those of HSPCs. Our data demonstrate that, despite the substantial impact of HIV-1 infection on CD4(+) T cells, HSPC repopulation remains polyclonal, thus supporting the use of HSPC transplant for anti-HIV treatment. American Association for the Advancement of Science 2020-07-22 /pmc/articles/PMC7385479/ /pubmed/32766447 http://dx.doi.org/10.1126/sciadv.aay9206 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Suryawanshi, Gajendra W.
Khamaikawin, Wannisa
Wen, Jing
Shimizu, Saki
Arokium, Hubert
Xie, Yiming
Wang, Eugene
Kim, Shihyoung
Choi, Hyewon
Zhang, Chong
Yu, Hannah
Presson, Angela P.
Kim, Namshin
An, Dong-Sung
Chen, Irvin S. Y.
Kim, Sanggu
The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title_full The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title_fullStr The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title_full_unstemmed The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title_short The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
title_sort clonal repopulation of hspc gene modified with anti–hiv-1 rnai is not affected by preexisting hiv-1 infection
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385479/
https://www.ncbi.nlm.nih.gov/pubmed/32766447
http://dx.doi.org/10.1126/sciadv.aay9206
work_keys_str_mv AT suryawanshigajendraw theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT khamaikawinwannisa theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT wenjing theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT shimizusaki theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT arokiumhubert theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT xieyiming theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT wangeugene theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimshihyoung theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT choihyewon theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT zhangchong theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT yuhannah theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT pressonangelap theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimnamshin theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT andongsung theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT chenirvinsy theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimsanggu theclonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT suryawanshigajendraw clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT khamaikawinwannisa clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT wenjing clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT shimizusaki clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT arokiumhubert clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT xieyiming clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT wangeugene clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimshihyoung clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT choihyewon clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT zhangchong clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT yuhannah clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT pressonangelap clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimnamshin clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT andongsung clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT chenirvinsy clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection
AT kimsanggu clonalrepopulationofhspcgenemodifiedwithantihiv1rnaiisnotaffectedbypreexistinghiv1infection