Cargando…

Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques

Cellular viral reservoirs are rapidly established in tissues upon HIV‐1/SIV infection, which persist throughout viral infection, even under long‐term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut‐associated lymphoid tissues (GALT) and inflamed tissues, w...

Descripción completa

Detalles Bibliográficos
Autores principales: Ziani, Widade, Shao, Jiasheng, Fang, Angela, Connolly, Patrick J., Wang, Xiaolei, Veazey, Ronald S., Xu, Huanbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839271/
https://www.ncbi.nlm.nih.gov/pubmed/33484474
http://dx.doi.org/10.1096/fj.202002235R
_version_ 1783643358561828864
author Ziani, Widade
Shao, Jiasheng
Fang, Angela
Connolly, Patrick J.
Wang, Xiaolei
Veazey, Ronald S.
Xu, Huanbin
author_facet Ziani, Widade
Shao, Jiasheng
Fang, Angela
Connolly, Patrick J.
Wang, Xiaolei
Veazey, Ronald S.
Xu, Huanbin
author_sort Ziani, Widade
collection PubMed
description Cellular viral reservoirs are rapidly established in tissues upon HIV‐1/SIV infection, which persist throughout viral infection, even under long‐term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut‐associated lymphoid tissues (GALT) and inflamed tissues, which may promote the seeding and dissemination of HIV‐1/SIV to these tissue sites. In this study, we investigated the efficacy of prophylactic integrin blockade (α4β7 antibody or α4β7/α4β1 dual antagonist TR‐14035) on viral infection, as well as dissemination and seeding of viral reservoirs in systemic and lymphoid compartments post‐SIV inoculation. The results showed that blockade of α4β7/α4β1 did not decrease viral infection, replication, or reduce viral reservoir size in tissues of rhesus macaques after SIV infection, as indicated by equivalent levels of plasma viremia and cell‐associated SIV RNA/DNA to controls. Surprisingly, TR‐14035 administration in acute SIV infection resulted in consistently higher viremia and more rapid disease progression. These findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV‐1/SIV infection. The use of integrin blockade for prevention or/and therapeutic strategies requires further investigation.
format Online
Article
Text
id pubmed-7839271
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-78392712021-03-03 Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques Ziani, Widade Shao, Jiasheng Fang, Angela Connolly, Patrick J. Wang, Xiaolei Veazey, Ronald S. Xu, Huanbin FASEB J Research Articles Cellular viral reservoirs are rapidly established in tissues upon HIV‐1/SIV infection, which persist throughout viral infection, even under long‐term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut‐associated lymphoid tissues (GALT) and inflamed tissues, which may promote the seeding and dissemination of HIV‐1/SIV to these tissue sites. In this study, we investigated the efficacy of prophylactic integrin blockade (α4β7 antibody or α4β7/α4β1 dual antagonist TR‐14035) on viral infection, as well as dissemination and seeding of viral reservoirs in systemic and lymphoid compartments post‐SIV inoculation. The results showed that blockade of α4β7/α4β1 did not decrease viral infection, replication, or reduce viral reservoir size in tissues of rhesus macaques after SIV infection, as indicated by equivalent levels of plasma viremia and cell‐associated SIV RNA/DNA to controls. Surprisingly, TR‐14035 administration in acute SIV infection resulted in consistently higher viremia and more rapid disease progression. These findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV‐1/SIV infection. The use of integrin blockade for prevention or/and therapeutic strategies requires further investigation. John Wiley and Sons Inc. 2021-01-23 2021-02 /pmc/articles/PMC7839271/ /pubmed/33484474 http://dx.doi.org/10.1096/fj.202002235R Text en © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Ziani, Widade
Shao, Jiasheng
Fang, Angela
Connolly, Patrick J.
Wang, Xiaolei
Veazey, Ronald S.
Xu, Huanbin
Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title_full Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title_fullStr Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title_full_unstemmed Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title_short Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
title_sort mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in siv‐infected rhesus macaques
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839271/
https://www.ncbi.nlm.nih.gov/pubmed/33484474
http://dx.doi.org/10.1096/fj.202002235R
work_keys_str_mv AT zianiwidade mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT shaojiasheng mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT fangangela mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT connollypatrickj mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT wangxiaolei mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT veazeyronalds mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques
AT xuhuanbin mucosalintegrina4b7blockadefailstoreducetheseedingandsizeofviralreservoirsinsivinfectedrhesusmacaques