The lysine methyltransferase SMYD5 amplifies HIV-1 transcription and is post-transcriptionally upregulated by Tat and USP11.

ABSTRACT: A successful HIV-1 cure strategy may require enhancing HIV-1 latency to silence HIV-1 transcription. Modulators of gene expression show promise as latency-promoting agents in vitro and in vivo. Here, we identify Su(var)3-9, enhancer-of-zeste, and trithorax (SET) and myeloid, Nervy, and DEAF-1 (MYND) domain-containing protein 5 (SMYD5) as a host factor required for HIV-1 transcription. SMYD5 is expressed in CD4⁺ T cells and activates the HIV-1 promoter with or without the viral Tat protein, while knockdown of SMYD5 decreases HIV-1 transcription in cell lines and primary T cells. SMYD5 associates in vivo with the HIV-1 promoter and binds the HIV trans-activation response (TAR) element RNA and Tat. Tat is methylated by SMYD5 in vitro, and in cells expressing Tat, SMYD5 protein leve

SUBMITTER: Boehm D 

PROVIDER: S-EPMC10124996 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature