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

Author

Listed:
  • Jun Niu

    (ShanghaiTech University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • 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
    Changping Laboratory)

  • Bei Yang

    (ShanghaiTech University
    Shanghai Clinical Research and Trial Center)

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.

Suggested Citation

  • 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 & Bei Yang, 2023. "Structures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40321-x
    DOI: 10.1038/s41467-023-40321-x
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