Extensive global HIV-1 sequence diversity perturbs conserved features of the envelope glycan shield

Abstract

The extensive sequence diversity and glycosylation of the HIV-1 envelope glycoprotein pose a challenge for vaccine design efforts aimed at eliciting glycan-binding broadly neutralizing antibodies (bnAbs). Understanding how HIV-1 glycosylation varies across diverse strains is therefore of considerable interest. Here, we employed mass spectrometry to map the site-specific glycan composition of pseudoviruses from an established 12-virus panel representing global sequence diversity. We refine the current model of the viral glycan shield by showing how the presence or absence of glycans can modulate the composition and perimeter of the mannose patch, where glycans exhibit limited maturation. Importantly, we show that within the Clade A 398F1 strain, isolated in Tanzania, the trimer apex exhibited elevated glycan maturation and resistance to apex-directed bnAbs. These findings demonstrate that the 12-virus panel reveals both conserved glycan-dependent epitopes and strains with exceptional glycosylation features that may impact the generality of vaccine design efforts targeting particular epitopes.