The interaction between the membrane-proximal external region and the N-trimer region of HIV-1 gp41: Involvement in viral fusion  

作　　者：LI Jing LU Lu WU Fan CHEN Xi NIU Ben JIANG ShiBo CHEN YingHua 

机构地区：[1]Laboratory of Immunology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China [2]Beijing Key Laboratory for Protein Therapeutics, Beijing 100084, China [3]Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA

出　　处：《Chinese Science Bulletin》2009年第10期1707-1712,共6页

基　　金：Supported by National Key Basic Research and Development Program of China (Grant No. 2007CB914402)

摘　　要：The membrane proximal external region (MPER) of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB interacted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif (WF) located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the fusion process between viral envelope and target cell membrane.The membrane proximal external region （MPER） of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide （D4E10P） with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB interacted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif （WF） located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the fusion process between viral envelope and target cell membrane.

关 键 词：GP41 病毒感染 外部区域 相互作用 三聚体 膜融合 HIV 抗原表位 

分 类 号：Q786[生物学—分子生物学] S858.28[农业科学—临床兽医学]