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02435 GP340: A NOVEL MICROBICIDE FROM THE INNATE IMMUNE SYSTEM Malamud, Daniel* Gp340 is a high molecular weight sialyated glycoprotein that inhibits HIV-1 infectivity in vitro. This protein is a member of the scavenger receptor cysteine-rich (SRCR) family found on the surface of many epithelial cells, and also secreted into bronchial alveolar lavage, tears, and saliva. Secreted forms lack a transmembrane domain. Gp340 appears to play a broad role in the innate immune system. We reported that gp340 inhibits a wide range of HIV-1 strains by interacting with viral gp120 in a calcium-dependent reaction. Gp340 binds to gp120 with a KD of 10-7 10-10 M, comparable to gp120-sCD4, but this binding occurs at a site distinct from CD4. The binding reaction is specifically inhibited by antibodies to gp340. We have now identified the binding sequence on the V3 loop of gp120 as a highly conserved site that is part of the CCR-5 binding region. We now report that while high level of gp340 are secreted at some locations (lung, eye, salivary gland), only modest levels are found in cervical-vaginal lavage. It appears that in cells of the reproductive tract, gp340 is expressed as a membrane associated protein. Our studies suggest that cell surface gp340 could function to concentrate and perhaps transmit virus, while soluble gp340 functions as an inhibitor of HIV-1 infectivity. We are currently exploring the possibility that truncated forms of soluble gp340 could be the basis for a novel microbicide. Dr. Daniel Malamud |
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