The gamma class chemokine Lymphotactin regulates T cell trafficking from blood to lymph nodes and is instrumental in recruiting cells to the mucosa. We are studying the structure and function of Lymphotactin to increase our comprehension of its biological functions and to devise rational design strategies to produce new drugs based on this molecule. We cloned cDNA for the rhesus and human Lymphotactin genes. The cDNA clones were expressed in E. coli and recombinant proteins were purified. The recombinant Lymphotactin was fully active in biological assays and we noted a species specificity wherein the rhesus molecule was at least five-times more active on rhesus cells than on human cells. A similar specificity was observed for human Lymphotactin. We have produced sufficient Lymphotactin and 15N-Lymphotactin for structural analysis by NMR and this effort is underway. In addition we have generated chimeric SHIV that express Lymphotactin in place of the nef gene. These viruses are stable during in vitro passages and we are preparing stocks for animal infection studies. FUTURE DIRECTIONS We are developing recombinant SHIV that express lymphotactin and these viruses will be tested for mucosal transmission efficiency. Additionally, we are developing assays for lymphotactin expression in vivo and for understanding the role of this chemokine in mucosal virus transmission and mucosal vaccine efficacy. KEY WORDS AIDS, chemokine, structure, lymphocyte, trafficking, vaccine FUNDING NIH R01 AI/RR42534
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