Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation
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, John C. Kappes, Joseph Sodroski
Abstract
The development of an efficient vaccine is critical for combating HIV-1 infection worldwide. However, the instability of the pretriggered shape (state 1) of the viral envelope glycoprotein (Env) makes it difficult to raise neutralizing antibodies against HIV-1. Here, by introducing multiple changes in Env, we derived two HIV-1 Env variants that are enriched in state 1 and can be efficiently cross-linked to maintain this shape. These Env complexes are more stable in detergent, assisting their purification. Thus, our study provides a path to a better characterization of the native pretriggered Env, which should assist vaccine development.