Nature microbiology, 2019-05, Vol.4 (5), p.813-825
2019
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- Autor(en) / Beteiligte
- Titel
- Proteomic profiling of HIV-1 infection of human CD4 + T cells identifies PSGL-1 as an HIV restriction factor
- Ist Teil von
- Nature microbiology, 2019-05, Vol.4 (5), p.813-825
- Ort / Verlag
- England
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 SCF . 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2058-5276eISSN: 2058-5276DOI: 10.1038/s41564-019-0372-2Titel-ID: cdi_pubmed_primary_30833724
- Format
- –
- Schlagworte
- CD4-Positive T-Lymphocytes - metabolism, CD4-Positive T-Lymphocytes - virology, HIV Infections - genetics, HIV Infections - metabolism, HIV Infections - physiopathology, HIV Infections - virology, HIV-1 - genetics, HIV-1 - physiology, Host-Pathogen Interactions, Human Immunodeficiency Virus Proteins - genetics, Human Immunodeficiency Virus Proteins - metabolism, Humans, Interferon-gamma - genetics, Interferon-gamma - metabolism, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Proteolysis, Proteomics, SKP Cullin F-Box Protein Ligases - genetics, SKP Cullin F-Box Protein Ligases - metabolism, Ubiquitination, Viral Regulatory and Accessory Proteins - genetics, Viral Regulatory and Accessory Proteins - metabolism