HIV-1 Envelope Glycan Composition as a Key Determinant of Efficient Virus Transmission via DC-SIGN and Resistance to Inhibitory Lectins

The HIV-1 envelope (Env) surface is shrouded with an assortment of oligomannose-, hybrid-, and complex-type glycans that enable virus interaction with carbohydrate-recognizing lectins. This study examined the importance of glycan heterogeneity for HIV-1 transmission through the trans-infection pathway by the host mannose-binding lectin DC-SIGN. A diversity of glycan content was observed among HIV-1 strains and associated with varying degrees of trans-infection via DC-SIGN and sensitivity to trans-infection blockage by antiviral lectins. When Env glycans were modified to display only the oligomannose type, DC-SIGN-mediated virus capture was enhanced; however, virus trans-infection was diminished because of increased degradation, which was alleviated by incorporation with hybrid-type glycans. Amino acid changes in the Env signal peptide (SP) modulated the Env glycan content, leading to alterations in DC-SIGN-dependent trans-infection and virus sensitivity to antiviral lectins. Hence, SP variation and glycosylation that confer varied types of oligosaccharides to HIV-1 Env are critical determinants for virus fitness and phenotypic diversity.