Differentiation into an Effector Memory Phenotype Potentiates HIV-1 Latency Reversal in CD4<sup>+</sup>T Cells
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- Deanna A. Kulpa
- Department of Pediatrics, Emory University, Atlanta, Georgia, USA
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- Aarthi Talla
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
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- Jessica H. Brehm
- ViiV Healthcare, Research Triangle Park, North Carolina, USA
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- Susan Pereira Ribeiro
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
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- Sally Yuan
- Janssen Pharmaceuticals, Springhouse, Pennsylvania, USA
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- Anne-Gaelle Bebin-Blackwell
- University of Georgia, Athens, Georgia, USA
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- Michael Miller
- Infectious Disease, Merck & Co., Inc., West Point, Pennsylvania, USA
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- Richard Barnard
- Infectious Disease, Merck & Co., Inc., West Point, Pennsylvania, USA
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- Steven G. Deeks
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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- Daria Hazuda
- Infectious Disease, Merck & Co., Inc., West Point, Pennsylvania, USA
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- Nicolas Chomont
- Centre de Recherche du CHUM, Montréal, Quebec, Canada
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- Rafick-Pierre Sékaly
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
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- Viviana Simon
- editor
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説明
<jats:p>By performing phenotypic analysis of latency reversal in CD4<jats:sup>+</jats:sup>T cells from virally suppressed individuals, we identify the T<jats:sub>EM</jats:sub>subset as the largest contributor to the inducible HIV reservoir. Differential responses of memory CD4<jats:sup>+</jats:sup>T cell subsets to latency-reversing agents (LRAs) demonstrate that HIV gene expression is associated with heightened expression of transcriptional pathways associated with differentiation, acquisition of effector function, and cell cycle entry.<jats:italic>In vitro</jats:italic>modeling of the latent HIV reservoir in memory CD4<jats:sup>+</jats:sup>T cell subsets identify LRAs that reverse latency with ranges of efficiency and specificity. We found that therapeutic induction of latency reversal is associated with upregulation of identical sets of T<jats:sub>EM</jats:sub>-associated genes and cell surface markers shown to be associated with latency reversal in our<jats:italic>ex vivo</jats:italic>and<jats:italic>in vitro</jats:italic>models. Together, these data support the idea that the effector memory phenotype supports HIV latency reversal in CD4<jats:sup>+</jats:sup>T cells.</jats:p>
収録刊行物
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- Journal of Virology
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Journal of Virology 93 (24), 2019-12
American Society for Microbiology
