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CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection

HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We...

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Autores principales: Baiyegunhi, Omolara O., Mann, Jaclyn, Khaba, Trevor, Nkosi, Thandeka, Mbatha, Anele, Ogunshola, Funsho, Chasara, Caroline, Ismail, Nasreen, Ngubane, Thandekile, Jajbhay, Ismail, Pansegrouw, Johan, Dong, Krista L., Walker, Bruce D., Ndung’u, Thumbi, Ndhlovu, Zaza M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279299/
https://www.ncbi.nlm.nih.gov/pubmed/35831418
http://dx.doi.org/10.1038/s41467-022-31692-8
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author Baiyegunhi, Omolara O.
Mann, Jaclyn
Khaba, Trevor
Nkosi, Thandeka
Mbatha, Anele
Ogunshola, Funsho
Chasara, Caroline
Ismail, Nasreen
Ngubane, Thandekile
Jajbhay, Ismail
Pansegrouw, Johan
Dong, Krista L.
Walker, Bruce D.
Ndung’u, Thumbi
Ndhlovu, Zaza M.
author_facet Baiyegunhi, Omolara O.
Mann, Jaclyn
Khaba, Trevor
Nkosi, Thandeka
Mbatha, Anele
Ogunshola, Funsho
Chasara, Caroline
Ismail, Nasreen
Ngubane, Thandekile
Jajbhay, Ismail
Pansegrouw, Johan
Dong, Krista L.
Walker, Bruce D.
Ndung’u, Thumbi
Ndhlovu, Zaza M.
author_sort Baiyegunhi, Omolara O.
collection PubMed
description HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3(+) T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8(+) T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.
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spelling pubmed-92792992022-07-15 CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection Baiyegunhi, Omolara O. Mann, Jaclyn Khaba, Trevor Nkosi, Thandeka Mbatha, Anele Ogunshola, Funsho Chasara, Caroline Ismail, Nasreen Ngubane, Thandekile Jajbhay, Ismail Pansegrouw, Johan Dong, Krista L. Walker, Bruce D. Ndung’u, Thumbi Ndhlovu, Zaza M. Nat Commun Article HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3(+) T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8(+) T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART. Nature Publishing Group UK 2022-07-12 /pmc/articles/PMC9279299/ /pubmed/35831418 http://dx.doi.org/10.1038/s41467-022-31692-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Baiyegunhi, Omolara O.
Mann, Jaclyn
Khaba, Trevor
Nkosi, Thandeka
Mbatha, Anele
Ogunshola, Funsho
Chasara, Caroline
Ismail, Nasreen
Ngubane, Thandekile
Jajbhay, Ismail
Pansegrouw, Johan
Dong, Krista L.
Walker, Bruce D.
Ndung’u, Thumbi
Ndhlovu, Zaza M.
CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title_full CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title_fullStr CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title_full_unstemmed CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title_short CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
title_sort cd8 lymphocytes mitigate hiv-1 persistence in lymph node follicular helper t cells during hyperacute-treated infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279299/
https://www.ncbi.nlm.nih.gov/pubmed/35831418
http://dx.doi.org/10.1038/s41467-022-31692-8
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