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Low-density lipoprotein receptor-related protein 1 mediates α1-antitrypsin internalization in CD4+ T lymphocytes.
Zhou, Xueyuan; Liu, Zhu; Shapiro, Leland; Yang, Jun; Burton, Gregory F.
Afiliación
  • Zhou X; *Clinic Services Program, Leidos Biomedical Research Inc., Frederick, Maryland, USA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA; Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, Haikou, Ha
  • Liu Z; *Clinic Services Program, Leidos Biomedical Research Inc., Frederick, Maryland, USA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA; Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, Haikou, Ha
  • Shapiro L; *Clinic Services Program, Leidos Biomedical Research Inc., Frederick, Maryland, USA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA; Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, Haikou, Ha
  • Yang J; *Clinic Services Program, Leidos Biomedical Research Inc., Frederick, Maryland, USA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA; Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, Haikou, Ha
  • Burton GF; *Clinic Services Program, Leidos Biomedical Research Inc., Frederick, Maryland, USA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA; Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, Haikou, Ha
J Leukoc Biol ; 98(6): 1027-35, 2015 Dec.
Article en En | MEDLINE | ID: mdl-26206901
In α1-antitrypsin-deficient HIV patients, an accelerated decline of CD4(+) T cell numbers is observed, suggesting that α1-antitrypsin is a potential endogenous HIV inhibitor. In infected T lymphocytes, α1-antitrypsin potently blocks NF-κB activation and HIV-1 replication by directly interacting with IκBα in the cytosol, thereby altering its ubiquitination pattern. However, the mechanism of α1-antitrypsin entry into the cytosol, where IκBα locates, remains unclear. In the present study, we investigated the mechanism of α1-antitrypsin internalization in CD4(+) T cells. Thus, primary CD4(+) T cells were infected with HIV-1 and then incubated with α1-antitrypsin to detect its internalization. We found that CD4(+) T cells internalized α1-antitrypsin through a clathrin-dependent endocytosis process. Next, intracellular α1-antitrypsin exerted the inhibitory effect on NF-κB activation and HIV-1 replication. On primary CD4(+) T cells, α1-antitrypsin interacted with low-density lipoprotein receptor-related protein 1 to initiate the internalization. Inside CD4(+) T lymphocytes, α1-antitrypsin was transported from the endosome to the lysosome and then released into the cytosol, where it is possible for α1-antitrypsin to directly interact with IκBα. These results together suggest that α1-antitrypsin internalization is a clathrin-dependent and low-density lipoprotein receptor-related protein 1-mediated endocytosis process. Internalized α1-antitrypsin is transported through the endosome-lysosome-cytosol routine to interact with cytosolic IκBα and block NF-κB activation and HIV-1 replication.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación Viral / Linfocitos T CD4-Positivos / Alfa 1-Antitripsina / VIH-1 / Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad Límite: Female / Humans / Male Idioma: En Revista: J Leukoc Biol Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación Viral / Linfocitos T CD4-Positivos / Alfa 1-Antitripsina / VIH-1 / Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad Límite: Female / Humans / Male Idioma: En Revista: J Leukoc Biol Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido