Identification of Genetically Intact HIV-1 Proviruses in Specific CD4 + T Cells from Effectively Treated Participants.

Autor:	Hiener B; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia. Electronic address: bonnie.hiener@sydney.edu.au., Horsburgh BA; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia., Eden JS; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia., Barton K; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia., Schlub TE; Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia., Lee E; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia., von Stockenstrom S; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Karolinska University Hospital, Stockholm 171 77, Sweden., Odevall L; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Karolinska University Hospital, Stockholm 171 77, Sweden., Milush JM; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Liegler T; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Sinclair E; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Hoh R; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Boritz EA; Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20814, USA., Douek D; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20814, USA., Fromentin R; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC H2X 0A9, Canada., Chomont N; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC H2X 0A9, Canada., Deeks SG; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Hecht FM; Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA., Palmer S; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Oct 17; Vol. 21 (3), pp. 813-822.
DOI:	10.1016/j.celrep.2017.09.081
Abstrakt:	Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4 + T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization. FLIPS provides a genome-scale perspective that addresses the limitations of other methods that also genetically characterize the latent reservoir. Using FLIPS, we identified 5% of proviruses as intact and potentially replication competent. Intact proviruses were unequally distributed between T cell subsets, with effector memory cells containing the largest proportion of genetically intact HIV-1 proviruses. We identified multiple identical intact proviruses, suggesting a role for cellular proliferation in the maintenance of the latent HIV-1 reservoir. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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