PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells

Yajing Fu, Sijia He, Abdul A. Waheed, Deemah Dabbagh, Zheng Zhou, Benjamin Trinité, Zhao Wang, Jieshi Yu, Dan Wang, Feng Li, David N. Levy, Hong Shang, Eric O. Freed, Yuntao Wu

Research output: Contribution to journalArticle

Abstract

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is expressed primarily on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits HIV-1 replication, the mechanism of PSGL-1-mediated anti-HIV activity remains to be elucidated. Here we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein or vesicular stomatitis virus G glycoprotein or even lacking a viral glycoprotein is impaired by PSGL-1. Mapping studies show that the extracellular N-terminal domain of PSGL-1 is necessary for its anti-HIV-1 activity, and that the PSGL-1 cytoplasmic tail contributes to inhibition. In addition, we demonstrate that the PSGL-1-related monomeric E-selectin-binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or expression of either Vpu or Nef, down-regulates PSGL-1 from the cell surface; expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1-mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses, such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a unique mechanism of action.

Original languageEnglish (US)
Pages (from-to)9537-9545
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number17
DOIs
StatePublished - Apr 28 2020

Keywords

  • CD43
  • HIV-1
  • Nef
  • PSGL-1
  • Vpu

ASJC Scopus subject areas

  • General

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  • Cite this

    Fu, Y., He, S., Waheed, A. A., Dabbagh, D., Zhou, Z., Trinité, B., Wang, Z., Yu, J., Wang, D., Li, F., Levy, D. N., Shang, H., Freed, E. O., & Wu, Y. (2020). PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells. Proceedings of the National Academy of Sciences of the United States of America, 117(17), 9537-9545. https://doi.org/10.1073/pnas.1916054117