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Updated: Jan 3, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
GADD34 attenuates HIV-1 replication by viral 5'-UTR TAR RNA-mediated translational inhibition
Mohammad Ishaq1, Heather Marshall1, Ven Natarajan1
1Laboratory of Molecular Cell Biology, Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD, 21702, USA.
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.
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