Viral and Host Mediators of Non-Suppressible HIV-1 Viremia.

Autor: Mohammadi A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Etemad B; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Zhang X; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Li Y; University of Pittsburgh, Pittsburgh, PA, USA., Bedwell GJ; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Sharaf R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Kittilson A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Melberg M; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Wong C; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Fajnzylber J; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Worrall DP; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Rosenthal A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jordan H; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jilg N; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Kaseke C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Giguel F; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Lian X; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Deo R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Gillespie E; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Chishti R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Abrha S; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Adams T; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Siagian A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Anderson PL; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Deeks SG; Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA., Lederman MM; Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Yawetz S; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Kuritzkes DR; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Lichterfeld MD; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Tsibris A; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Carrington M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Brumme ZL; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada., Castillo-Mancilla JR; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Engelman AN; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Gaiha GD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA., Li JZ; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 Mar 31. Date of Electronic Publication: 2023 Mar 31.
DOI: 10.1101/2023.03.30.23287124
Abstrakt: Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as "producer", and those that did not as "non-producer". Compared to ART-suppressed individuals, NSV participants had a significantly larger producer reservoir. Producer proviruses were enriched in chromosome 19 and in proximity to the activating H3K36me3 epigenetic mark. CD4 + cells from NSV participants demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, NSV participants showed no elevation in HIV-specific CD8 + cell responses and producer proviruses were enriched for HLA escape mutations. We identified critical host and viral mediators of NSV that represent potential targets to disrupt HIV persistence and promote viral silencing.
Databáze: MEDLINE