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

Autor: Hogan LE; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Vasquez J; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Hobbs KS; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Hanhauser E; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Aguilar-Rodriguez B; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Hussien R; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Thanh C; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Gibson EA; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Carvidi AB; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Smith LCB; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Khan S; Virology and Immunology, Gladstone Institutes, San Francisco, California, United States of America., Trapecar M; Virology and Immunology, Gladstone Institutes, San Francisco, California, United States of America., Sanjabi S; Virology and Immunology, Gladstone Institutes, San Francisco, California, United States of America.; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, United States of America., Somsouk M; Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Stoddart CA; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America., Kuritzkes DR; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., Deeks SG; Positive Health Program, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Henrich TJ; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2018 Feb 22; Vol. 14 (2), pp. e1006856. Date of Electronic Publication: 2018 Feb 22 (Print Publication: 2018).
DOI: 10.1371/journal.ppat.1006856
Abstrakt: 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.
Databáze: MEDLINE
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