Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice.

Autor:	Mangala Prasad V; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Leaman DP; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Lovendahl KN; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Croft JT; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Benhaim MA; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Hodge EA; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Zwick MB; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: zwick@scripps.edu., Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA; Biological Physics, Structure and Design Graduate Program, University of Washington, Seattle, WA 98195, USA; Department of Microbiology, University of Washington, Seattle, WA 98195, USA. Electronic address: kklee@uw.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2022 Feb 17; Vol. 185 (4), pp. 641-653.e17. Date of Electronic Publication: 2022 Feb 04.
DOI:	10.1016/j.cell.2022.01.013
Abstrakt:	HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here, we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1-Å sub-tomogram-averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers, and a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation. Competing Interests: Declaration of interests Authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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