translation agency

NLM AIDSLINE
Cutting edge: SIV Nef protein utilizes both leucine- and tyrosine-based protein sorting pathways for down-regulation of CD4.
Bresnahan PA; Yonemoto W; Greene WC; Gladstone Institute of Virology,
December 30, 1999
J Immunol. 1999 Sep 15;163(6):2977-81. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Animal Antigens, CD4/*BIOSYNTHESIS Antigens, CD8/GENETICS Cell Line Chimeric Proteins/BIOSYNTHESIS/METABOLISM Down-Regulation (Physiology)/GENETICS/*IMMUNOLOGY DNA-Binding Proteins/METABOLISM Gene Products, nef/GENETICS/*IMMUNOLOGY Human HIV-1/GENETICS/IMMUNOLOGY Leucine/GENETICS/*METABOLISM Macaca Membrane Proteins/METABOLISM Mutagenesis, Site-Directed Signal Transduction/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. SIV/GENETICS/*IMMUNOLOGY Transcription Factors/METABOLISM Tyrosine/GENETICS/*METABOLISM

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