National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI140868
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM099989
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI143563
米国
引用
ジャーナル: Cell / 年: 2022 タイトル: Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice. 著者: Vidya Mangala Prasad / Daniel P Leaman / Klaus N Lovendahl / Jacob T Croft / Mark A Benhaim / Edgar A Hodge / Michael B Zwick / Kelly K Lee / 要旨: 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 ...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.