作者
Hanh T Nguyen, Alessandra Qualizza, Saumya Anang, Meiqing Zhao, Shitao Zou, Rong Zhou, Qian Wang, Shijian Zhang, Ashlesha Deshpande, Haitao Ding, Ta-Jung Chiu, Amos B Smith III, John C Kappes, Joseph G Sodroski
发表日期
2022/4/27
期刊
Journal of Virology
卷号
96
期号
8
页码范围
e01668-21
出版商
American Society for Microbiology
简介
Binding to the receptor, CD4, drives the pretriggered, “closed” (state-1) conformation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer into more “open” conformations (states 2 and 3). Broadly neutralizing antibodies, which are elicited inefficiently, mostly recognize the state-1 Env conformation, whereas the more commonly elicited poorly neutralizing antibodies recognize states 2/3. HIV-1 Env metastability has created challenges for defining the state-1 structure and developing immunogens mimicking this labile conformation. The availability of functional state-1 Envs that can be efficiently cross-linked at lysine and/or acidic amino acid residues might assist these endeavors. To that end, we modified HIV-1AD8 Env, which exhibits an intermediate level of triggerability by CD4. We introduced lysine/acidic residues at positions that exhibit such polymorphisms in natural HIV-1 strains …
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