The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template

Andrabi, Raiees; Pallesen, Jesper; Allen, Joel D.; Song, Ge; Zhang, Jinsong; de Val, Natalia; Gegg, Gavin; Porter, Katelyn; Su, Ching-Yao; Pauthner, Matthias; Newman, Amanda; Bouton-Verville, Hilary; Garces, Fernando; Wilson, Ian A.; Crispin, Max; Hahn, Beatrice H.; Haynes, Barton F.; Verkoczy, Laurent; Ward, Andrew B.; Burton, Dennis R.

We solved the structure of the MT145K trimer by cryo-EM to a global resolution of 4.1 Ã… ( Figure S2 ; Table S1 ). To date, our structure represents the only atomic-level structure of an SIV Env trimer. Like other class I fusion proteins, protomers (gp120 and gp41) of MT145K trimerize to form a metastable pre-fusion Env trimer (Figures 2A, 2B , and S3) (Kwon et al., 2015; McLellan et al., 2013; Pallesen et al., 2016 Pallesen et al., , 2017 Stevens et al., 2004) . The trimer architecture exhibits a mushroom-like shape with subunits gp120 and gp41 constituting the envelope-distal and proximal entities, respectively ( Figure 2B ). Overall, the MT145K trimer configuration closely resembles that of the trimeric HIV Env spike, with an overall Ca root-mean-square deviation (RMSD) of 1.9 Ã… (Kwon et al., 2015) . The arrangement of the V loops in the MT145K Env trimer is reminiscent of the V-loop arrangement in the HIV Env trimer and is suggestive of a similar role in immune evasion by steric occlusion of underlying conserved epitopes (Julien et al., 2013a; Pancera et al., 2014) . Notably, the V1 and V2 loops are largely solvent exposed and occlude access to the underlying V3 loop ( Figure 2C ). Inaccessibility of the V3 loop is mediated by intra-protomer interactions of V1V2 to V3 and by extensive inter-protomer V1V2 trimer interactions at the apex of the spike. The SIV MT145K Env trimer exhibited well-ordered V2-V5 loops, while V1 is somewhat disordered ( Figure 2D ).