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

Abstract：

: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.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Sung JA,Sholtis K,Kirchherr J,Kuruc JD,Gay CL,Nordstrom JL,Bollard CM,Archin NM,Margolis DM

doi

10.1016/j.ebiom.2017.07.019

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

52-58

issn

2352-3964

pii

S2352-3964(17)30292-X

journal_volume

23

pub_type

杂志文章

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