Department of Molecular Virology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
Department of Molecular Virology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
Microbes Infect. 2018 Jun-Jul;20(6):346-352. doi: 10.1016/j.micinf.2018.05.001. Epub 2018 May 26.
Host factors are required for efficient HIV-1 replication. To identify these factors, genome-wide RNA interference screening was performed using a human T cell line. In the present study, we assessed whether eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), a DEAD-box protein identified in our screen, is necessary for efficient HIV-1 replication. Exploiting MT4C5 cells depleted of eIF4A2 by stable expression of eIF4A2-specific short-hairpin RNA (shRNA) using a lentiviral system, we found that depletion of eIF4A2 markedly inhibited the infection of a replication-competent reporter HIV-1. eIF4A2 depletion reduced the efficiency of viral cDNA synthesis with virion entry into target cells being unaffected. Depletion of eIF4A2 also inhibited HIV-1 spreading infection in a knockdown level-dependent manner. These results suggest that HIV-1 requires eIF4A2 for optimal replication in human T cells.
宿主因素是 HIV-1 复制所必需的。为了鉴定这些因素，我们使用人 T 细胞系进行了全基因组 RNA 干扰筛选。在本研究中，我们评估了 DEAD 盒蛋白 eIF4A2 是否是我们筛选中鉴定出的、HIV-1 复制所必需的有效因子。利用慢病毒系统稳定表达 eIF4A2 特异性短发夹 RNA (shRNA) 使 MT4C5 细胞中 eIF4A2 耗竭，我们发现 eIF4A2 的耗竭显著抑制了复制型报告 HIV-1 的感染。eIF4A2 的耗竭降低了病毒 cDNA 合成的效率，而病毒进入靶细胞的效率不受影响。eIF4A2 的耗竭也以依赖敲低水平的方式抑制 HIV-1 的扩散感染。这些结果表明，HIV-1 在人 T 细胞中复制需要 eIF4A2。
