6OHY

Chimpanzee SIV Env trimeric ectodomain.

Summary for 6OHY

• Entry DOI: 10.2210/pdb6ohy/pdb
• EMDB information: 20074
• Descriptor: Envelope glycoprotein gp160, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: hiv, cimpanzee, siv, env, envelope, gp120, gp41, trimer, glycoprotein, simian, immunodeficiency, virus, vaccine., viral protein
• Biological source: Simian immunodeficiency virus (SIV); More
• Total number of polymer chains: 6
• Total formula weight: 231984.21

Authors

Pallesen, J.,Andrabi, R.,de Val, N.,Burton, D.R.,Ward, A.B. (deposition date: 2019-04-08, release date: 2019-06-05, Last modification date: 2024-10-09)

Primary citation

Andrabi, R.,Pallesen, J.,Allen, J.D.,Song, G.,Zhang, J.,de Val, N.,Gegg, G.,Porter, K.,Su, C.Y.,Pauthner, M.,Newman, A.,Bouton-Verville, H.,Garces, F.,Wilson, I.A.,Crispin, M.,Hahn, B.H.,Haynes, B.F.,Verkoczy, L.,Ward, A.B.,Burton, D.R.
The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.
Cell Rep, 27:2426-2441.e6, 2019

PubMed Abstract: Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.

PubMed: 31116986
DOI: 10.1016/j.celrep.2019.04.082

Experimental method

ELECTRON MICROSCOPY (4.1 Å)