GADD34 attenuates HIV-1 replication by viral 5'-UTR TAR RNA-mediated translational inhibition.

GADD34 attenuates HIV-1 replication by viral 5'-UTR TAR RNA-mediated translational inhibition.
Virology. 2019 Nov 15;540:119-131
Authors: Ishaq M, Marshall H, Natarajan V
Abstract
Role of GADD34, a protein that is induced following cellular stress, in HIV-1 replication was investigated. GADD34 was induced during the late phase of HIV-1 infection. siRNA-knockdown of GADD34 stimulated whereas overexpression of GADD34 inhibited HIV-1 replication. GADD34 N-terminal ER-binding-helix amino acid region 1-192 alone was found to be sufficient for the inhibition of HIV-1 replication whereas protein-phosphatase -1-binding domain and eIF-2α-phosphatase activity of GADD34 were not crucial for anti-HIV-1 activity. GADD34 did not alter the HIV-1 RNA levels but reduced the viral protein expression suggesting that GADD34 interferes in HIV protein synthesis. Studies on the effect of HIV-1-5'-UTR and its mutants on a human promoter-driven luciferase expression indicated that GADD34-inhibition was mediated by 5'-UTR/TAR RNA, probably by modulating TAR RNA structure. In summary, our data support a novel function of GADD34 as a putative anti-HIV-1 restriction factor.
PMID: 31778897 [PubMed - as supplied by publisher]

Source: Virology - November 14, 2019 Category: Virology Authors: Ishaq M, Marshall H, Natarajan V Tags: Virology Source Type: research