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Nat Microbiol. 2019 Mar 4. doi: 10.1038/s41564-019-0372-2. [Epub ahead of print]

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

Author information

1
MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
2
Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.
3
School of System Biology, George Mason University, Manassas, VA, USA.
4
Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
5
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
6
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
7
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
8
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
9
Beijing You'an Hospital, Capital Medical University, Beijing, China.
10
Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. zhou_feng@fudan.edu.cn.
11
School of System Biology, George Mason University, Manassas, VA, USA. ywu8@gmu.edu.
12
MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China. xutan@tsinghua.edu.cn.

Abstract

Human immunodeficiency virus (HIV) actively modulates the protein stability of host cells to optimize viral replication. To systematically examine this modulation in HIV infection, we used isobaric tag-based mass spectrometry to quantify changes in the abundance of over 14,000 proteins during HIV-1 infection of human primary CD4+ T cells. We identified P-selectin glycoprotein ligand 1 (PSGL-1) as an HIV-1 restriction factor downregulated by HIV-1 Vpu, which binds to PSGL-1 and induces its ubiquitination and degradation through the ubiquitin ligase SCFβ-TrCP2. PSGL-1 is induced by interferon-γ in activated CD4+ T cells to inhibit HIV-1 reverse transcription and potently block viral infectivity by incorporating in progeny virions. This infectivity block is antagonized by Vpu via PSGL-1 degradation. We further show that PSGL-1 knockdown can significantly abolish the anti-HIV activity of interferon-γ in primary CD4+ T cells. Our study identifies an HIV restriction factor and a key mediator of interferon-γ's anti-HIV activity.

PMID:
30833724
DOI:
10.1038/s41564-019-0372-2

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