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-Structure paper
タイトル | Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 5236, Year 2022 |
掲載日 | 2022年9月6日 |
著者 | Fangzhu Zhao / Zachary T Berndsen / Nuria Pedreño-Lopez / Alison Burns / Joel D Allen / Shawn Barman / Wen-Hsin Lee / Srirupa Chakraborty / Sandrasegaram Gnanakaran / Leigh M Sewall / Gabriel Ozorowski / Oliver Limbo / Ge Song / Peter Yong / Sean Callaghan / Jessica Coppola / Kim L Weisgrau / Jeffrey D Lifson / Rebecca Nedellec / Thomas B Voigt / Fernanda Laurino / Johan Louw / Brandon C Rosen / Michael Ricciardi / Max Crispin / Ronald C Desrosiers / Eva G Rakasz / David I Watkins / Raiees Andrabi / Andrew B Ward / Dennis R Burton / Devin Sok / |
PubMed 要旨 | SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing ...SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model. |
リンク | Nat Commun / PubMed:36068229 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.47 - 30.0 Å |
構造データ | EMDB-25621, PDB-7t2p: EMDB-25623: SIVmac239.K180S SOSIP in complex with FZ019.2 Fab EMDB-25624: SIVmac239.K180S SOSIP in complex with FZ012.7 Fab EMDB-25625: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque Rh33519 EMDB-25626: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque Rh31186 EMDB-25627: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque Rh34620 EMDB-25628: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque r11008 EMDB-25629: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque r11008 EMDB-25630: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque r11002 EMDB-25631: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque r11004 EMDB-25632: SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque r11004 EMDB-25676, PDB-7t4g: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SIV / Env / vaccine / neutralizing antibody / glycoprotein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |