Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells

被引:23
作者
Sung, Julia A. [1 ,2 ]
Sholtis, Katherine [1 ,2 ]
Kirchherr, Jennifer [1 ,2 ]
Kuruc, Joann D. [1 ,2 ]
Gay, Cynthia L. [1 ,2 ]
Nordstrom, Jeffrey L. [5 ]
Bollard, Catherine M. [6 ]
Archin, Nancie M. [1 ,2 ]
Margolis, David M. [1 ,2 ,3 ,4 ]
机构
[1] Univ North Carolina Chapel Hill, UNC HIV Cure Ctr, Chapel Hill, NC 27599 USA
[2] Univ North Carolina Chapel Hill, Dept Med, Chapel Hill, NC 27599 USA
[3] Univ North Carolina Chapel Hill, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[4] Univ North Carolina Chapel Hill, UNC Ctr AIDS Res, Chapel Hill, NC 27599 USA
[5] MacroGenics Inc, Rockville, MD 20850 USA
[6] Childrens Natl Med Ctr, Dept Cellular Therapy, Washington, DC 20010 USA
基金
美国国家卫生研究院;
关键词
HIV; Latency; Eradication; Vorinostat; Immune effector; ANTIRETROVIRAL THERAPY; IN-VIVO; INFECTION; REACTIVATION; PROVIRUSES; INHIBITOR; VIREMIA; ESCAPE;
D O I
10.1016/j.ebiom.2017.07.019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period. Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART)-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms. (C) 2017 The Authors. Published by Elsevier B.V.
引用
收藏
页码:52 / 58
页数:7
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