SYNDECAN AGONISTS AND ANTAGONISTS AS MICROBICIDES

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Syndecans are mammalian cell surface proteins that are believed to be involved in HIV infection of cells. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. One of these, syndecan 1 is a heparin sulfate molecule that antibodies have been made against in an attempt to utilize this approach for microbicide development. Our collaborators from Scripps Res Institute have found that blocking syndecans on the surface of cells with specific anti-syndecan antibody fragments (Fab syndecan antagonists) prevents attachment and transport of HIV through mucosal cell monolayers and can prevent HIV infection and growth in cells in vitro. Since syndecan receptors on the cell surface are also involved in attachment and transport of other sexually transmitted diseases (i.e., herpes and gonorrhea) this approach has an advantage over HIV specific microbicides, as it may prevent several sexually transmitted diseases in addition to HIV. However, in preliminary testing, these agonists or antagonists neither protected macaques against vaginal SHIV Transmission.