Doms Robert W
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
Top HIV Med. 2004 Oct-Nov;12(4):100-3.
HIV entry to host cells begins with binding of the viral envelope protein to CD4 molecules on the host cell surface. This binding initiates conformational changes in the envelope protein that result in binding to a coreceptor (CCR5 or CXCR4), exposure of a previously hidden domain in the viral protein, insertion of a viral fusion peptide into the host-cell membrane and fusing the viral and cell membranes. Each of these steps provides an opportunity for intervention to prevent viral entry, and a number of agents targeting these steps are in development. Studies of coreceptor inhibitors and fusion inhibitors have indicated the presence of host and viral factors that can result in variability of antiretroviral effect. Improved understanding of these factors will help to guide clinical use of these new agents. This article summarizes a presentation by Robert W. Doms, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.
HIV进入宿主细胞始于病毒包膜蛋白与宿主细胞表面的CD4分子结合。这种结合引发包膜蛋白的构象变化，导致其与共受体（CCR5或CXCR4）结合，暴露病毒蛋白中先前隐藏的结构域，将病毒融合肽插入宿主细胞膜，并使病毒膜与细胞膜融合。这些步骤中的每一步都为干预以防止病毒进入提供了机会，并且许多针对这些步骤的药物正在研发中。对共受体抑制剂和融合抑制剂的研究表明，存在可导致抗逆转录病毒效果变异性的宿主和病毒因素。对这些因素的深入了解将有助于指导这些新药的临床应用。本文总结了医学博士、哲学博士罗伯特·W·多姆斯于2004年5月在芝加哥举行的美国国际艾滋病学会课程上的一次演讲。
