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

  • Nat Microbiol. 2019 May;4(5):813-825. doi: 10.1038/s41564-019-0372-2.
Ying Liu   #  1 ,  Yajing Fu   #  2  3 ,  Qian Wang  4 ,  Mushan Li  5 ,  Zheng Zhou  3 ,  Deemah Dabbagh  3 ,  Chunyan Fu  1 ,  Hang Zhang  1 ,  Shuo Li  1 ,  Tengjiang Zhang  1 ,  Jing Gong  1 ,  Xiaohui Kong  1 ,  Weiwei Zhai  6  7 ,  Jiaming Su  8 ,  Jianping Sun  9 ,  Yonghong Zhang  9 ,  Xiao-Fang Yu  8 ,  Zhen Shao  5 ,  Feng Zhou  10 ,  Yuntao Wu  11 ,  Xu Tan  12
Affiliations
  • 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. [email protected].
  • 11. School of System Biology, George Mason University, Manassas, VA, USA. [email protected].
  • 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. [email protected].
  • # Contributed equally.
PMID: 30833724 DOI: 10.1038/s41564-019-0372-2
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.

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