Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
Florent Colomb,
Leila B. Giron,
Leticia Kuri-Cervantes,
Opeyemi S. Adeniji,
Tongcui Ma,
Harsh Dweep,
Emilie Battivelli,
Eric Verdin,
Clovis S. Palmer,
Hiroaki Tateno,
Andrew V. Kossenkov,
Nadia R. Roan,
Michael R. Betts,
Mohamed Abdel-Mohsen
Affiliations
Florent Colomb
The Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA
Leila B. Giron
The Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA
Leticia Kuri-Cervantes
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA
Opeyemi S. Adeniji
The Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA
Tongcui Ma
University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA
Harsh Dweep
The Wistar Institute, Philadelphia, PA 19104, USA
Emilie Battivelli
The Buck Institute for Research on Aging, Novato, CA 94945, USA
Eric Verdin
The Buck Institute for Research on Aging, Novato, CA 94945, USA
Clovis S. Palmer
The Burnet Institute, Melbourne, VIC 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, VIC 3004, Australia
Hiroaki Tateno
National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
Andrew V. Kossenkov
The Wistar Institute, Philadelphia, PA 19104, USA
Nadia R. Roan
University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA
Michael R. Betts
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA
Mohamed Abdel-Mohsen
The Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Summary: 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-LewisX (SLeX), compared with 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. 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.
