PAX2 expression by HHV-8–infected endothelial cells induced a proangiogenic and proinvasive phenotype

Human Herpesvirus 8 (HHV8), is considered the primary etiologic agent of Kaposi’s sarcoma (KS) as HHV8 infected endothelial cells acquire a KS-like phenotype. In the present study we evaluated whether the infection of microvascular endothelial cells (HMEC) with HHV8 can trigger the expression of PAX2 oncogene and whether Pax2 protein is involved in HHV8-induced transformation of HMEC. We found that HHV8 infection induced the expression of both the PAX2 gene and Pax2 protein in HMEC but failed to induce Pax2 protein in HMEC stably transfected with PAX2 antisense (HMEC-AS). HHV8-infected HMEC but not HMEC-AS acquired proinvasive and proadhesive properties and enhanced survival and in vitro angiogenesis suggesting a correlation between Pax2 expression and the effects triggered by HHV8 infection. When HMEC expressing Pax2 by stably transfection with PAX2 sense gene or by HHV8 infection were implanted in vivo in SCID mice, enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV8 infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These results suggest that the expression of Pax2 is required for the proangiogenic and proinvasive changes induced by HHV8 infection in HMEC. In conclusion, HHV8 infection may activate an embryonic angiogenic program in HMEC by inducing the expression of PAX2 oncogene.