Kaposi’s sarcoma (KS) is a human malignancy associated with Kaposi’s sarcoma-associated herpesvirus (KSHV). KS continue to be the most common HIV-associated cancer world-wide. KS lesions are characterized by proliferating endothelial-derived spindle cells, leaky blood vessels, and inflammatory infiltrating leukocytes. Within these lesions, inflammatory leukocytes secret cytokines and growth factors that KSHV-infected cells rely on for growth and survival. KSHVinfected endothelial cells promote the infiltration of inflammatory cells by modulating the expression of adhesion factors on its surface. We have found that KSHV infection induces the expression of novel endothelial adhesion factors and increases leukocyte adhesion and transendothelial migration. We propose to determine the mechanism by which KSHV induces leukocyte adhesion and transendothelial migration and validate the biology of this process using tissue specimens from the AIDS and Cancer Specimen Resource (ACSR). Our proposal will also identify new targets for therapies against KS in HIV-infection individuals.