Sialyl-Lewis(X) Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy

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.