Barnor Jacob Samson, Miyano-Kurosaki Naoko, Yamaguchi Kazuya, Sakamoto Atsushi, Ishikawa Koichi, Inagaki Yoshio, Yamamoto Naoki, Osei-Kwasi Mubarak, Ofori-Adjei David, Takaku Hiroshi
Department of Life and Environmental Science, 2-17-1 Tsudanuma, 275-0016 Narashino, Chiba, Japan.
Biochem Biophys Res Commun. 2004 Jul 23;320(2):544-50. doi: 10.1016/j.bbrc.2004.05.201.
The human immunodeficiency virus type-1 (HIV-1)-encoded vif protein is essential for viral replication, virion production, and pathogenicity. HIV-1 vif interacts with the endogenous human APOBEC3G protein (an mRNA editor) in target cells to prevent its virions from encapsidation. Although some studies have established targets within the HIV-1 vif gene that are important for its biologic function, it is however important to further screen for effective therapeutic targets in the vif gene that could interfere with the HIV-1 vif-dependent infectivity and pathogenicity. This report demonstrates that HIV-1 vif antisense RNA fragments constructed within mid-3' region, notably the region spanning nucleic acid positions 5561-5705 (M-3'-AS), significantly inhibited HIV-1 replication in MT-4 and H9-infected cells and reduced the HIV-1 vif mRNA transcripts. These data clearly suggest that the above vif fragment, which corresponds to amino acid residues 96-144, could be an effective novel therapeutic target site for gene therapy applications, for the control and management of HIV-1 infection, due to its strong inhibition of HIV-1 replication in cells.
1型人类免疫缺陷病毒（HIV-1）编码的病毒感染因子（vif）蛋白对病毒复制、病毒体产生及致病性至关重要。HIV-1 vif在靶细胞中与内源性人类载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G，一种mRNA编辑酶）相互作用，以防止其病毒体被包装。尽管一些研究已确定HIV-1 vif基因内对其生物学功能重要的靶点，但进一步筛选vif基因中可干扰HIV-1 vif依赖性感染性和致病性的有效治疗靶点仍很重要。本报告表明，在3'区域中部构建的HIV-1 vif反义RNA片段，特别是跨越核酸位置5561 - 5705的区域（M-3'-AS），可显著抑制MT-4细胞和H9感染细胞中的HIV-1复制，并减少HIV-1 vif mRNA转录本。这些数据清楚地表明，上述对应于氨基酸残基96 - 144的vif片段，因其对细胞中HIV-1复制的强烈抑制作用，可能是基因治疗应用中用于控制和管理HIV-1感染的有效新型治疗靶点。
