Induction of chemokine production by latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells

Abstract

Infection with Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is linked strongly to development of KS, an endothelial neoplasm also characterized by striking neoangiogenesis and infiltration with inflammatory cells. To elucidate the links between endothelial infection and inflammation, primary human umbilical vein endothelial cells (HUVECs) were examined for the production of chemokines following latent KSHV infection. Several chemokines that are produced in the ground state, including MCP-1, NAP 2 and RANTES, are upregulated significantly by KSHV infection. Moreover, the chemokine CXCL16, which is nearly absent in uninfected cells, is induced significantly following infection. This induction is attributable primarily to expression of vFLIP, a known inducer of NF-kappaB. CXCL16 induces the chemotaxis of activated T cells, whose products have been proposed to positively regulate KS tumour-cell survival and growth. Whilst CXCL16 has also been proposed as a direct endothelial chemoattractant and mitogen, neither proliferation nor chemotaxis of HUVECs was observed following CXCL16 exposure. These results suggest that CXCL16 induction by KSHV contributes to the inflammatory phenotype of KS, but plays little role in the recruitment of endothelial spindle cells.