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.

中文翻译：

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GADD34通过病毒5'-UTR TAR RNA介导的翻译抑制作用来减弱HIV-1复制。

研究了GADD34（一种受细胞压力后诱导的蛋白质）在HIV-1复制中的作用。GADD34在HIV-1感染的晚期被诱导。刺激GADD34的siRNA敲低，而GADD34的过表达抑制HIV-1复制。发现单独的GADD34 N端ER结合螺旋氨基酸区域1-192足以抑制HIV-1复制，而GADD34的蛋白磷酸酶-1-结合域和eIF-2α-磷酸酶活性并不关键抗HIV-1活性。GADD34不会改变HIV-1 RNA的水平，但会降低病毒蛋白的表达，提示GADD34会干扰HIV蛋白的合成。研究HIV-1-5'-UTR及其突变体对人启动子驱动的萤光素酶表达的影响，表明GADD34抑制作用是由5'-UTR / TAR RNA介导的，可能是通过调节TAR RNA结构。总之，我们的数据支持GADD34作为抗HIV-1限制因子的新功能。