Abstract
The Nef protein is unique to primate lentiviruses and is closely linked to accelerated pathogenesis in both human and monkey hosts. Nef acts to down-regulate CD4 and MHC class I, two receptors important for immune function. A recent report demonstrated the presence of two tyrosine motifs in SIV Nef that contribute to its ability to down-regulate CD4 and to associate with clathrin adaptors. These tyrosine motifs are not present in HIV-1 Nef, which instead utilizes a leucine-based motif for its down-regulation of CD4. We now report that SIV Nef also contains a conserved leucine-based motif that contributes to CD4 down-regulation, functions to stimulate internalization, and contributes to the association of SIV Nef with clathrin adaptors AP-1 and AP-2. These results demonstrate that SIV Nef differs from HIV-1 Nef by its ability to use two parallel pathways of the protein-sorting machinery based on either tyrosine or leucine motifs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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Animals
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CD4 Antigens / biosynthesis*
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CD8 Antigens / genetics
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Cell Line
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DNA-Binding Proteins / metabolism
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Gene Products, nef / genetics
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Gene Products, nef / immunology*
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HIV-1 / genetics
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HIV-1 / immunology
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Humans
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Leucine / genetics
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Leucine / metabolism*
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Macaca
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Membrane Proteins / metabolism
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Mutagenesis, Site-Directed
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / immunology
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Simian Immunodeficiency Virus / genetics
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Simian Immunodeficiency Virus / immunology*
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Transcription Factor AP-2
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Transcription Factors / metabolism
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Tyrosine / genetics
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Tyrosine / metabolism*
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nef Gene Products, Human Immunodeficiency Virus
Substances
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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CD4 Antigens
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CD8 Antigens
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DNA-Binding Proteins
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Gene Products, nef
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Membrane Proteins
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Recombinant Fusion Proteins
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Transcription Factor AP-2
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Transcription Factors
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nef Gene Products, Human Immunodeficiency Virus
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Tyrosine
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Leucine