THE ROLE OF INTRACELLULAR TRAFFIC IN HIV INFECTION

一项关于CD4的研究，被认为是人类的t细胞受体

An investigation of CD4, the presumed T-cell receptor for the human immunodeficiency virus, has shown that surface expression of this protei is blocked by tunicamycin, a potent inhibitor of glycosylation, under conditions where alternate surface receptors are unaffected. Initial studies employing acute lymphoblastic leukemic cells have beer extended by the successful transfection of a plasmid containing the cDNA For CD4 into Chinese hamster ovary cells. Subsequent cotransfection with another plasmid containing the multiple drug resistant gene, has permitted the isolation of stable clones expressing large amounts of CD4. Preliminary data on this material indicates the presence in CD4 of complex or multi- antennary hybrid oligosaccharides. A targeting sequence has been identified which is sufficient to allow protein molecules as large as 0.5 x 10 to pass through the nuclear envelope. This has been assessed in our laboratory by chemically coupling peptides having the nuclear localization sequence to a highly fluorescent cytoplasmic protein. The sequence Pro-Lys-Lys-Lys-Arg-Lys-Va-Cys is sufficient to target these conjugates to the nucleus. The tat and art gene products of HIV have sequences very similar to this targeting domain. The approach we have taken is to chemically synthesize peptides corresponding to the tat sequence examined the ability of this peptide to confer nuclear localization. In addition to these studies, we have begun to examine the structure of the nuclear pore complex, across which the many nucleocytoplasmic exchange processes must occur. The structure of the pore complex is explored using recombinant DNA techniques. The major nuclear pore glycoprotein np62 has been cloned and a large segment sequenced.