Heterogeneity in glycan composition on the surface of HIV-1 envelope determines virus sensitivity to lectins—JAN 2018

Antiviral lectins target HIV-1 envelope (Env) glycoprotein N-glycans. Although lectin and Env glycan interaction has been deciphered, more research is needed to understand HIV-1 isolate Env glycosylation heterogeneity and its effect on virus-neutralization sensitivity to lectins. This study tested a panel of lectins with fine specificity for different oligosaccharides to prevent HIV-1 viral infection. HIV-1 isolates react differently to lectins binding α1-3Man, α1-6Man, and α1-2Man. These findings show that HIV-1 isolates' glycan variability may explain this differential sensitivity. Lectins only identify viral Env's oligosaccharides. To test this, chronic and acute viruses were created with various glycosidase inhibitors to express homogeneous glycans. α1-2Man-binding lectins also affected viruses with enhanced Man5-9GlcNAc2 glycans. The α1-3Man- and α1-6Man-binding lectins were more effective against viruses expressing primarily Man5GlcNAc2 and hybrid type glycans with terminal α1-3Man and α1-6Man. Mannan and viral enrichment of mannose-type glycans competitively reduced lectin-mediated inhibition. HIV-1 Env glycans are heterogeneous, with complex, hybrid, and mannose types. Viruses richer in mannose-type glycans were vulnerable to Endo-H deglycosylation, although untreated viruses were somewhat resistant. Due to N-linked glycosylation microheterogeneity on the virus Env glycoprotein, HIV-1 isolates have variable lectin sensitivity.

Jan, M., Upadhyay, C., Alcami Pertejo, J., Hioe, C. E., & Arora, S. K. (2018). Heterogeneity in glycan composition on the surface of HIV-1 envelope determines virus sensitivity to lectins. PloS one, 13(3), e0194498. https://doi.org/10.1371/journal.pone.0194498