Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two proteins that are similar to human CC chemokines and a G protein-coupled receptor (KSHV-GPCR) that is constitutively active. KSHV-GPCR binds a number of human CXC and CC chemokines. We showed that interferon gamma-inducible protein-10 (IP-10), a human CXC chemokine, inhibits KSHV-GPCR signaling (Geras-Raaka et al., J. Exp. Med. 188, 405-408, 1998). Here we show that viral monocyte inflammatory protein-II (vMIP-II), one of the KSHV-encoded CC chemokines, and stromal cell-derived factor 1alpha (SDF-1alpha), a human CXC chemokine that blocks infection by human immunodeficiency virus-type 1, inhibit KSHV-GPCR signaling also. If KSHV-GPCR signaling is involved in viral pathogenesis, then these chemokines may affect the course of Kaposi's sarcoma and primary effusion lymphoma.
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