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.

The remarkable conservation in the overall architecture of the chimpanzee SIV and HIV Env glycan shield, despite sharing only 62% of the amino-acid sequence identity, suggests that the glycan shield has an indispensable role in immune evasion and potentially maintaining the functional integrity of the trimer spike. Indeed, the glycan shield is integral to all lentiviral envelopes and appears to have evolved somewhat specifically to mammalian hosts ( Figure S4 ). Over the course of lentiviral evolution, the Env glycan density shows an overall gradual progression and likely peaked in retroviruses infecting non-human primates and plateaued in HIV Envs ( Figure S4 ) (Zhang et al., 2004) . Therefore, the high-density Env glycan shield on HIV must have been established well before chimpanzee SIV crossed into humans. Nevertheless, several glycan positions on HIV Env appear to have subtly shifted after the species crossover: presumably as a result of adaptation to the human immune system ( Figure S5 ).