当前位置： SCI文献检索 > Cell Reports期刊下所有文献 > In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a "Block-and-Lock" Strategy for HIV-1 Treatment.

In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a "Block-and-Lock" Strategy for HIV-1 Treatment.

Abstract：

:HIV-1 Tat activates viral transcription and limited Tat transactivation correlates with latency establishment. We postulated a "block-and-lock" functional cure approach based on properties of the Tat inhibitor didehydro-Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia during antiretroviral therapy (ART), locking the HIV promoter in persistent latency. We investigated this hypothesis in human CD4+ T cells isolated from aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation. We show that dCA mediates epigenetic silencing by increasing nucleosomal occupancy at Nucleosome-1, restricting RNAPII recruitment to the HIV-1 promoter. The efficacy of dCA was studied in the bone marrow-liver-thymus (BLT) mouse model of HIV latency and persistence. Adding dCA to ART-suppressed mice systemically reduces viral mRNA in tissues. Moreover, dCA significantly delays and reduces viral rebound levels upon treatment interruption. Altogether, this work demonstrates the potential of block-and-lock cure strategies.

journal_name

Cell Rep

journal_title

Cell reports

authors

Kessing CF,Nixon CC,Li C,Tsai P,Takata H,Mousseau G,Ho PT,Honeycutt JB,Fallahi M,Trautmann L,Garcia JV,Valente ST

doi

10.1016/j.celrep.2017.09.080

subject

Has Abstract

pub_date

2017-10-17 00:00:00

pages

600-611

issue

3

issn

2211-1247

pii

S2211-1247(17)31385-2

journal_volume

21

pub_type

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