Masuda Takao
Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Uirusu. 2011 Jun;61(1):73-80. doi: 10.2222/jsv.61.73.
Reverse transcription of retroviral RNA into double stranded DNA is a characteristic feature of rertoviruses including human immunodeficiency virus type I (HIV-1). There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. Here, we summarized recent our studies demonstrating direct functional roles of IN and its binding partner of host factor, Gemin2 in the reverse transcription. We established new in vitro cell-free assay to mimic natural reverse transcription and found that HIV-1 IN and host factor, Gemin2 synergistically stimulate reverse transcriptase (RT) activity. Analysis of intracellular stability and multimer formation of IN suggest that that high-ordered structures, especially tetramer formation of IN is critical for the function. In addition, Gemin2 might have a role to keep the higher-order structure of IN. Thus, we provide new aspects of reverse transcription of HIV-1 through IN and host factors in addition to RT.
逆转录病毒RNA逆转录为双链DNA是包括人类免疫缺陷病毒1型（HIV-1）在内的逆转录病毒的一个特征。越来越多的证据表明逆转录病毒整合酶（IN）参与病毒RNA的逆转录。在此，我们总结了我们最近的研究，这些研究证明了IN及其宿主因子结合伙伴Gemin2在逆转录中的直接功能作用。我们建立了新的体外无细胞测定法来模拟自然逆转录，发现HIV-1 IN和宿主因子Gemin2协同刺激逆转录酶（RT）活性。对IN的细胞内稳定性和多聚体形成的分析表明，高阶结构，特别是IN的四聚体形成对其功能至关重要。此外，Gemin2可能在维持IN的高阶结构方面发挥作用。因此，除了RT之外，我们还通过IN和宿主因子提供了HIV-1逆转录的新方面。
