EMD-25625
SIVmac239.K180S SOSIP in complex with an unknown Fab from the polyclonal serum of the SIV-infected Rhesus Macaque Rh33519
EMD-25625
Single-particle30.0 Å
Deposition: 06/12/2021
Map released: 19/10/2022
Last modified: 17/01/2024
Sample Organism:
Simian immunodeficiency virus
Sample: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
Deposition Authors: Berndsen ZT , Lee W
Sample: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
Deposition Authors: Berndsen ZT , Lee W
Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.
Zhao F ,
Berndsen ZT ,
Pedreno-Lopez N ,
Burns A,
Allen JD ,
Barman S ,
Lee WH ,
Chakraborty S,
Gnanakaran S ,
Sewall LM,
Ozorowski G ,
Limbo O ,
Song G ,
Yong P ,
Callaghan S ,
Coppola J,
Weisgrau KL,
Lifson JD,
Nedellec R,
Voigt TB ,
Laurino F,
Louw J,
Rosen BC,
Ricciardi M ,
Crispin M ,
Desrosiers RC,
Rakasz EG ,
Watkins DI,
Andrabi R ,
Ward AB ,
Burton DR ,
Sok D
(2022) Nat Commun , 13 , 5236 - 5236
(2022) Nat Commun , 13 , 5236 - 5236
Abstract:
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.
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.