Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.

HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly en...

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Autores principales:	Louise E Hogan, Joshua Vasquez, Kristen S Hobbs, Emily Hanhauser, Brandon Aguilar-Rodriguez, Rajaa Hussien, Cassandra Thanh, Erica A Gibson, Alexander B Carvidi, Louis C B Smith, Shahzada Khan, Martin Trapecar, Shomyseh Sanjabi, Ma Somsouk, Cheryl A Stoddart, Daniel R Kuritzkes, Steven G Deeks, Timothy J Henrich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2018
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5f48aaf0ac6f4de885d57506c67f973f
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spelling	oai:doaj.org-article:5f48aaf0ac6f4de885d57506c67f973f2021-12-02T19:59:40ZIncreased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.1553-73661553-737410.1371/journal.ppat.1006856https://doaj.org/article/5f48aaf0ac6f4de885d57506c67f973f2018-02-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1006856https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+ lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection.Louise E HoganJoshua VasquezKristen S HobbsEmily HanhauserBrandon Aguilar-RodriguezRajaa HussienCassandra ThanhErica A GibsonAlexander B CarvidiLouis C B SmithShahzada KhanMartin TrapecarShomyseh SanjabiMa SomsoukCheryl A StoddartDaniel R KuritzkesSteven G DeeksTimothy J HenrichPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 14, Iss 2, p e1006856 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Louise E Hogan Joshua Vasquez Kristen S Hobbs Emily Hanhauser Brandon Aguilar-Rodriguez Rajaa Hussien Cassandra Thanh Erica A Gibson Alexander B Carvidi Louis C B Smith Shahzada Khan Martin Trapecar Shomyseh Sanjabi Ma Somsouk Cheryl A Stoddart Daniel R Kuritzkes Steven G Deeks Timothy J Henrich Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
description	HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+ lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection.
format	article
author	Louise E Hogan Joshua Vasquez Kristen S Hobbs Emily Hanhauser Brandon Aguilar-Rodriguez Rajaa Hussien Cassandra Thanh Erica A Gibson Alexander B Carvidi Louis C B Smith Shahzada Khan Martin Trapecar Shomyseh Sanjabi Ma Somsouk Cheryl A Stoddart Daniel R Kuritzkes Steven G Deeks Timothy J Henrich
author_facet	Louise E Hogan Joshua Vasquez Kristen S Hobbs Emily Hanhauser Brandon Aguilar-Rodriguez Rajaa Hussien Cassandra Thanh Erica A Gibson Alexander B Carvidi Louis C B Smith Shahzada Khan Martin Trapecar Shomyseh Sanjabi Ma Somsouk Cheryl A Stoddart Daniel R Kuritzkes Steven G Deeks Timothy J Henrich
author_sort	Louise E Hogan
title	Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
title_short	Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
title_full	Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
title_fullStr	Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
title_full_unstemmed	Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.
title_sort	increased hiv-1 transcriptional activity and infectious burden in peripheral blood and gut-associated cd4+ t cells expressing cd30.
publisher	Public Library of Science (PLoS)
publishDate	2018
url	https://doaj.org/article/5f48aaf0ac6f4de885d57506c67f973f
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Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30.

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