Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes—Upadhyay 2020

HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers produced from gp160, which has an ER-targeting signal peptide (SP) at its amino-terminus. ~90 N-linked glycans—complex-type and oligomannose-type—wrap each trimer and determine virus sensitivity to neutralizing antibodies. We studied Env characteristics and functionalities after single point SP alterations. We swapped SPs to study how SP variety affects glycosylation of viral-derived Env and virus neutralization. SP switching changed Env glycan concentration and occupancy on numerous N-linked glycosites, including preserved N156 and N160 in the V1V2 region at the trimer apex and N88 at the trimer base. V1V2, V3, and gp41 antibodies influenced virus neutralization. SP swaps also altered antibody recognition of soluble and cell-associated Env by V1V2 configurations, V3 crown, and gp41 epitopes. These findings demonstrate how SP sequence diversity affects Env glycan content and V1V2 and other Env epitope configuration and accessibility.

Upadhyay, C., Feyznezhad, R., Cao, L., Chan, K. W., Liu, K., Yang, W., Zhang, H., Yolitz, J., Arthos, J., Nadas, A., Kong, X. P., Zolla-Pazner, S., & Hioe, C. E. (2020). Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes. PLoS pathogens, 16(12), e1009185. https://doi.org/10.1371/journal.ppat.1009185