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

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 relat...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2020-08-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720309761
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author 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
author_facet 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
author_sort Florent Colomb
collection DOAJ
description 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.
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spelling doaj.art-7a931a3a4ffc4ff0895673a8784b27432022-12-22T01:08:12ZengElsevierCell Reports2211-12472020-08-01325107991Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during TherapyFlorent Colomb0Leila B. Giron1Leticia Kuri-Cervantes2Opeyemi S. Adeniji3Tongcui Ma4Harsh Dweep5Emilie Battivelli6Eric Verdin7Clovis S. Palmer8Hiroaki Tateno9Andrew V. Kossenkov10Nadia R. Roan11Michael R. Betts12Mohamed Abdel-Mohsen13The Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USAThe Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USADepartment 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, USAThe Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USAUniversity of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USAThe Wistar Institute, Philadelphia, PA 19104, USAThe Buck Institute for Research on Aging, Novato, CA 94945, USAThe Buck Institute for Research on Aging, Novato, CA 94945, USAThe Burnet Institute, Melbourne, VIC 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, VIC 3004, AustraliaNational Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, JapanThe Wistar Institute, Philadelphia, PA 19104, USAUniversity of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USADepartment 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, USAThe Wistar Institute, Philadelphia, PA 19104, USA; Penn Center for AIDS Research (Penn CFAR), University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720309761HIV persistenceHIV transcriptionglycosylationfucoseSialyl-LewisXT cell trafficking
spellingShingle 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
Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
Cell Reports
HIV persistence
HIV transcription
glycosylation
fucose
Sialyl-LewisX
T cell trafficking
title Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
title_full Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
title_fullStr Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
title_full_unstemmed Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
title_short Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
title_sort sialyl lewisx glycoantigen is enriched on cells with persistent hiv transcription during therapy
topic HIV persistence
HIV transcription
glycosylation
fucose
Sialyl-LewisX
T cell trafficking
url http://www.sciencedirect.com/science/article/pii/S2211124720309761
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