Dr. Alkhatib's laboratory is interested in the molecular determinants involved in fusion and entry of human retroviruses into susceptible cells. Understanding how the virus interacts with the host cell is necessary for developing reagents that may block virus infection. A series of discoveries made in 1996 concluded that human immunodeficiency virus type 1 (HIV-1) entry into host cells requires, in addition to the CD4 surface antigen, the co-expression of a certain chemokine receptor. CXCR4 is the coreceptor for T cell line-tropic HIV-1 isolates while CCR5 serves as a coreceptor for macrophage-tropic HIV-1. The coreceptors are members of the G protein-coupled receptor superfamily and are predicted to have seven hydrophobic transmembrane domains connected by alternating intracellular and extracellular loops. Using hybrid coreceptor constructs, Dr. Alkhatib as well as other investigators in the field demonstrated that G-protein signaling is not required for HIV-1 coreceptor activity and suggested the involvement of multiple extracellular domains of the chemokine receptor in envelope (En)-mediated cell fusion. His laboratory continues to characterize and map the Env interaction site(s) on the newly discovered HIV coreceptors. The main area of his research focuses on Env/CD4/coreceptor interaction and the analysis of the specificity of this interaction. His laboratory is also developing a screening strategy for isolating the cellular receptor for human T-cell lymphotropic virus type 1 (HTLV-1), the first characterized human tumor retrovirus and the cause of adult T-cell leukemia/lymphoma (ATLL), an aggressive and fatal malignancy of CD4+ T lymphocytes.
