Proteomic profiling of HIV-1 infection of human CD4+ T cells identifies PSGL-1 as an HIV restriction factor

Liu, Ying; Fu, Yajing; Wang, Qian; Li, Mushan; Zhou, Zheng; Dabbagh, Deemah; Fu, Chenbo; Zhang, Hang; Li, Shuo; Zhang, Tengjiang; Gong, Jing; Kong, Xiangkai; Zhai, Weiwei; Su, Jiaming; Sun, Jianping; Zhang, Yonghong; Yu, Xiaofang; Shao, Zongping; Zhou, Feng; Wu, Yuntao; Tan, Xu

doi:10.1038/s41564-019-0372-2

Cited by 54 publications

(92 citation statements)

References 48 publications

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“…Nevertheless, resting T cells can be latently infected and support low levels of HIV replication in the presence of cytokines such as IL-7 (14,15). It is possible that HIV infection of primary resting CD4 T cells may down-regulate PSGL-1, as seen in transformed T cell lines (12,16) (SI Appendix, Fig. S2).…”

Section: Resultsmentioning

confidence: 99%

“…Vpu has been identified as a viral factor that mediates intracellular PSGL-1 degradation (12). However, both Vpu and Nef are known broad-spectrum modulators of cell-surface receptors (16)(17)(18).…”

Section: Resultsmentioning

confidence: 99%

“…PSGL-1 also serves as a surface receptor for enterovirus 71 (EV71) infection of leukocytes (10). In a mouse model of chronic viral infection, PSGL-1 has been reported to regulate T cell checkpoints (11) and has been shown to be an IFN-γ-regulated factor involved in Th1-mediated antiviral activity (8,12). During T cell differentiation, culturing T cells in the Th1 cytokine IFN-γ and IL-12 promoted PSGL-1 expression preferentially in the IFNγ-producing T cell population (8), suggesting that PSGL-1 could be an IFN-γ-regulated factor involved in Th1-mediated antiviral activity.…”

mentioning

confidence: 99%

“…PSGL-1 has been reported to cocluster with HIV-1 Gag at sites of assembly in the T cell uropod in Gag-expressing cells (13). In addition, PSGL-1 was recently identified, through proteomic profiling of HIV-1-infected T cells, as an IFN-γ-induced restriction factor that blocks HIV-1 reverse transcription early postentry and inactivates progeny virion infectivity during viral assembly (12). The anti-HIV-1 activity of PSGL-1 also has been shown to be antagonized by the HIV-1 accessory protein Vpu (12); however, Vpu-mediated PSGL-1 down-regulation occurs only after reverse transcription and Vpu expression.…”

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confidence: 99%

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

Waheed

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Waheed

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…PSGL-1 binds to the selectin family of proteins, P-, E-, and L-selectin [2][3][4] , and mediates immune cell tethering and rolling on the surface of endothelium to promote cell migration into inflamed tissues [5][6][7][8] . In the context of viral infection, PSGL-1 has been identified as an IFN-γ-regulated inhibitory factor involved in blocking HIV-1 infectivity 7,9 , and was recently found to possess broad-spectrum antiviral activity 1 , blocking viral infections through steric hindrance of particle attachment to target cells 1,10 .…”

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PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity

Waheed

Hetrick

et al. 2020

Preprint

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P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that virion incorporation of PSGL-1 on SARS-CoV and SARS-CoV-2 pseudovirions blocks S protein-mediated virus attachment and infection of target cells. These findings suggest that PSGL-1-imprinted non-infectious viral particles could serve as a live attenuated vaccine for SARS-CoV-2 infection.was not certified by peer review)

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Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

Zheng

et al. 2022

The Anatomical Record

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HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS‐INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS‐INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS‐INRs. In our study, to identify the typical HIV/AIDS‐INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography–tandem mass spectrometry (TMT‐LC–MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome‐specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs‐INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS‐INRs.

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Proteomic profiling of HIV-1 infection of human CD4+ T cells identifies PSGL-1 as an HIV restriction factor

Cited by 54 publications

References 48 publications

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

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

PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

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