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

Cell Rep. 2020 Aug 4;32(5):107991. doi: 10.1016/j.celrep.2020.107991.

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-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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Carbohydrates / chemistry
  • Cell Line
  • Cell Membrane / metabolism
  • Fucose / metabolism
  • Glycomics
  • Glycosylation
  • HIV / genetics*
  • HIV Infections / immunology
  • Humans
  • Immunologic Memory
  • Ligands
  • Lymphocyte Activation / immunology
  • Sialyl Lewis X Antigen / metabolism*
  • Transcription, Genetic*

Substances

  • Carbohydrates
  • Ligands
  • Sialyl Lewis X Antigen
  • Fucose