it was very close to the therapeutic concentration

We did not identify significant US28 transcripts in HepG2 cells infected BAY 11-7082 with live and UV inactivated HCMV, To assess the extent of HCMV inactivation by UV treatment, we infected MRC 5 with UV treated virus. We discovered that UV treatment almost completely removed IE1 expression and virus infectivity, Taken together, these data suggest that the induction of IL 6 was at least in part determined by viral replication cycle in HCMV infected HepG2 cells and PHH. HCMV induces IL 6 mediated JAK STAT3 activation in HepG2 cells and PHH IL 6 binds to the IL 6 receptor to activate STAT3 signaling, Thus we considered the phosphorylation status of STAT3 in HepG2 cells and PHH infected with HCMV. not avoid STAT3 activation in PHH infected with HCMV, showing that STAT3 activation, like IL 6 production, do require early steps of viral replication. Since cytokine activation of STAT3 is mediated by upstream Janus kinases, we examined the expression of JAK 1 and JAK 2 in HepG2 cells and PHH infected with HCMV. JAK one andor JAK 2 activation was enhanced in HepG2 cells and PHH infected with AD169 or HCMV DB Metastatic carcinoma in comparison to mock infected cells, Pretreatment of HCMV infected HepG2 cells and PHH with a pot JAK inhibitor and a STAT3 inhibitor considerably decreased STAT3 phosphorylation, indicating activation of a JAK STAT3 axis in HepG2 cells and PHH infected with HCMV. Because the binding of IL 6 to IL 6R activates STAT3, we directly examined the role of IL 6R in STAT3 activation in HepG2 cells and PHH. HCMV infection induced STAT3 activation in both cell types, whereas incubation of HCMV infected cells with an IL 6R neutralizing OC000459 antibody decreased STAT3 phosphoryla tion, In contrast, incubation with an EGF receptor neutralizing antibody didn't inhibit STAT3 activation by HCMV in HepG2 cells, Moreover, incubation of cells with the recombinant glycoprotein gB, which was formerly,demonstrated to bind to and activate EGFR mediated pathways, didn't activate STAT3, In contrast to infection with live HCMV, decreased activation of STAT3 and JAK2 was observed in cells treated with UV inactivated HCMV, Our results indicate that in HepG2 cells and in PHH, HCMV induced STAT3 activation was mediated by autocrine andor paracrine IL 6 generation.