THE ANTI-ALPHA-4/BETA-7 MONOCLONAL ANTIBODY PROJECT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the earliest organ affected by HIV and SIV infection is the GI tract. Moreover, the bulk of viral replication occurs in this compartment leading to rapid and permanenet elimination of CD4+ T cells, in particular those co expresing the viral co-receptor CCR5. What is not clear to date is whether the continuous viral replication requires a constant influx of new CD4 targets or not, which would open a novel therapeutic vista by blockign traffic of potential target cells to the gut. Traffic to various organs appears to be dictated via a series of receptors, chemokines and cytokines, which in concert are able to ensure a regular replenishment of select lineages within a given compartment. Among the molecules dictating traffic to the gut the heterodimeric integrin ¿4¿7 has gained particular attention especially in the therapy of gut inflammatory syndromes such as IBD, UC and Crohn's Disease. The use of an ¿4¿7 blocking agent has thus far not been tested in the context of lentivurs infection, which is the purpose of this study. Thanks to the availability of a primatized monoclonal antibody specific to ¿4¿7we propose to block this traffic during acute and chronic SIV infection in efforts to determine the outcome of such blockade on virus replication/dissemination, viral immune responses and ultimately disease progression.