Structures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs

Jun Niu, Qi Wang, Wenwen Zhao, Bing Meng, Youwei Xu, Xianfang Zhang, Yi Feng, Qilian Qi, Yanling Hao, Xuan Zhang, Ying Liu, Jiangchao Xiang, Yiming Shao () and Bei Yang ()
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Jun Niu: ShanghaiTech University
Qi Wang: ShanghaiTech University
Wenwen Zhao: ShanghaiTech University
Bing Meng: ShanghaiTech University
Youwei Xu: ShanghaiTech University
Xianfang Zhang: ShanghaiTech University
Yi Feng: Chinese Center for Disease Control and Prevention
Qilian Qi: ShanghaiTech University
Yanling Hao: Chinese Center for Disease Control and Prevention
Xuan Zhang: ShanghaiTech University
Ying Liu: Chinese Center for Disease Control and Prevention
Jiangchao Xiang: ShanghaiTech University
Yiming Shao: Chinese Center for Disease Control and Prevention
Bei Yang: ShanghaiTech University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Structure-guided immunofocusing HIV-1 vaccine design entails a comprehensive understanding of Envs from diverse HIV-1 subtypes, including circulating recombinant forms (CRFs). Here, we present the cryo-EM structures of Envs from two Asia prevalent CRFs (CRF01_AE and CRF07_BC) at 3.0 and 3.5 Å. We compare the structures and glycosylation patterns of Envs from different subtypes and perform cross-clade statistical analyses to reveal the unique features of CRF01_AE V1 region, which are associated with the resistance to certain bNAbs. We also solve a 4.1 Å cryo-EM structure of CRF01_AE Env in complex with F6, the first bNAb from CRF01_AE-infected individuals. F6 recognizes a gp120-gp41 spanning epitope to allosterically destabilize the Env trimer apex and weaken inter-protomer packing, which in turn hinders the receptor binding and induces Env trimer disassembly, demonstrating a dual mechanism of neutralization. These findings broaden our understanding of CRF Envs and shed lights on immunofocusing HIV-1 vaccine design.

Date: 2023
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DOI: 10.1038/s41467-023-40321-x

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