HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer.

While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. SLBR-N was demonstrated to capture HIV-1 virions, bind to O-glycans on HIV-1 Env, and augment CD4 binding to Env. Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. Enhancing effects were recapitulated with O-glycan-binding plant lectins. Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa.