Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1–dependent capillary-like structure formation: role of the IKK/NF-κB pathway

• Published in: Blood 2007-04, Vol.109 (7), p.2718-2726
• Main Authors: Caselli, Elisabetta, Fiorentini, Simona, Amici, Carla, Di Luca, Dario, Caruso, Arnaldo, Santoro, M. Gabriella
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Medical sciences
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-03-012500

Human herpesvirus 8 (HHV-8) is considered the causative agent of Kaposi sarcoma, a highly vascularized neoplasm characterized by spindle-shaped cells of endothelial origin and inflammatory cell infiltration. The cell transforming ability of HHV-8 has been associated with the activation of NF-κB, a nuclear factor playing a pivotal role in promoting inflammation and cell proliferation; however, little is known about NF-κB activation during acute HHV-8 infection. In the present study, we used a recently established in vitro model of HHV-8 acute productive infection in endothelial cells to investigate the effect of HHV-8 on NF-κB activity and function. HHV-8 rapidly and potently induced NF-κB activity in endothelial cells via stimulation of the IκB kinase (IKK). Following IKK activation, HHV-8 selectively triggered the production of high levels of monocyte chemoattractant protein 1 (MCP-1), whereas it did not affect the expression of other NF-κB–dependent proinflammatory proteins, including TNF-α, IL-8, and RANTES. Deletion of NF-κB–binding sites in the MCP-1 enhancer resulted in significant inhibition of HHV-8–induced transcription. Furthermore, MCP-1 production was accompanied by virus-induced capillary-like structure formation at early stages of infection. The results suggest that HHV-8–induced MCP-1 may play an important role in promoting inflammation and pathogenic angiogenesis typical of HHV-8–associated lesions.