Sialyl-Lewis-X Glyco-antigen Is Enriched on Cells with Persistent HIV Transcription During Therapy
A comprehensive understanding of the phenotype of persistent HIV-infected cells, both transcriptionally-active and/or -inactive, is imperative for developing a cure. The relevance of cell-surface glycosylation to HIV persistence has never been explored. We characterized the relationship between cell-surface glycomic signatures and persistent HIV transcription in vivo. We found 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 (SLeX), compared to HIV-infected transcriptionally-inactive cells. These high levels of SLeX are induced by HIV transcription in vitro and are maintained after therapy in vivo. Cells with high SLeX are enriched with markers associated with HIV susceptibility, signaling pathways that drive HIV transcription, and pathways involved in leukocyte extravasation. Together, we describe a novel glycomic signature of HIV-infected transcriptionally-active cells that not only differentiates them from their transcriptionally-inactive counterparts, but also can impact their trafficking abilities. Overall design: RNA-seq of high and low SLEX cells