HIV-1 Nef Downregulates MHC-I by a PACS-1- and PI3K-Regulated ARF6 Endocytic Pathway
摘要：
The HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the trans-Golgi network (TGN) enables HIV-1 to escape immune surveillance. However, the cellular pathway used by Nef to downregulate MHC-I is unknown. Here, we show that Nef and PACS-1 combine to usurp the ARF6 endocytic pathway by a PI3K-dependent process and downregulate cell surface MHC-I to the TGN. This mechanism requires the hierarchical actions of three Nef motifs—the acidic cluster 62EEEE 65, the SH3 domain binding site 72PXXP 75, and M 20—in controlling PACS-1-dependent sorting to the TGN, ARF6 activation, and sequestering internalized MHC-I to the TGN, respectively. These data provide new insights into the cellular basis of HIV-1 immunoevasion.
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关键词：
Humans Cell Line Hela Cells Tumor Cells, Cultured Gene Products, nef Vesicular Transport Proteins Microscopy, Fluorescence Temperature Protein Structure, Tertiary src Homology Domains
DOI：
10.1016/S0092-8674(02)01162-5
被引量：
年份：
2003
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