Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy

Abstract

A comprehensive understanding of the phenotype of persistent HIV-infected cells, transcriptionally active and/or transcriptionally inactive, is imperative for developing a cure. The relevance of cell-surface glycosylation to HIV persistence has never been explored. We characterize the relationship between cell-surface glycomic signatures and persistent HIV transcription in vivo. We find that the cell surface of CD4⁺ T cells actively transcribing HIV, despite suppressive therapy, harbors high levels of fucosylated carbohydrate ligands, including the cell extravasation mediator Sialyl-Lewis^X (SLe^X), compared with HIV-infected transcriptionally inactive cells. These high levels of SLe^X are induced by HIV transcription in vitro and are maintained after therapy in vivo. Cells with high-SLe^X are enriched with markers associated with HIV susceptibility, signaling pathways that drive HIV transcription, and pathways involved in leukocyte extravasation. We describe a glycomic feature of HIV-infected transcriptionally active cells that not only differentiates them from their transcriptionally inactive counterparts but also may affect their trafficking abilities.

Keywords: HIV persistence; HIV transcription; Sialyl-Lewis(X); T cell trafficking; cutaneous lymphocyte antigen; fucose; glycosylation.