Nature immunology, 2019-06, Vol.20 (6), p.711-723
2019
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Details
- Autor(en) / Beteiligte
- Titel
- Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4 + T cells by degrading viral Gag polyprotein
- Ist Teil von
- Nature immunology, 2019-06, Vol.20 (6), p.711-723
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Resting CD4 T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4 T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4 T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4 T cells. TRABD2A expression was much higher in resting CD4 T cells than in activated CD4 T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4 T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4 T cells to potently restrict the assembly and production of HIV-1 progeny.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/s41590-019-0385-2Titel-ID: cdi_pubmed_primary_31061530
- Format
- –
- Schlagworte
- Animals, Cations, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, Cell Line, Enzyme Activation, gag Gene Products, Human Immunodeficiency Virus - metabolism, Gene Expression, HIV Infections - genetics, HIV Infections - immunology, HIV Infections - virology, HIV-1 - physiology, Host-Pathogen Interactions - genetics, Host-Pathogen Interactions - immunology, Humans, Membrane Proteins - metabolism, Metalloproteases - antagonists & inhibitors, Metalloproteases - genetics, Metalloproteases - metabolism, Multigene Family, Proteolysis, SAM Domain and HD Domain-Containing Protein 1 - genetics, SAM Domain and HD Domain-Containing Protein 1 - metabolism, Viral Load, Virus Replication