Human papillomavirus type 16 E7 impairs the activation of the interferon regulatory factor-1

We had previously observed that HPV-16 E7 disturbs the Guanylate Binding Pr otein (GBP)-ISRE reporter activation by IFN-gamma thus suggesting an altera tion of the IRF-1 function. In this study we examined the mechanism by whic h E7 affects the IFN-gamma signals driving the activation of gene transcrip tion. Using 14/2 BRK cells containing dexamethasone-inducible HPV-16 E7 gen e, we observed a large inhibition of the IRF-1 DNA binding activity upon E7 induction. Concomitantly, there was no significant change in the levels of IRF-1, indicating that this was not due to reduced levels of IRF-1 express ion. Likewise, in vitro translated E7 did not affect the IRF-1 DNA binding activity in nuclear extracts derived from IFN-induced cells, thus indicatin g that the effects of E7 are upstream of IRF-1's binding to its DNA recogni tion site. Finally, NF kappa B DNA binding activity was also inhibited unde r conditional expression of E7. These data indicate that HPV-16 E7 inhibits the IRF-1 and NF kappa B function and this could lead to the impairment of the IFN response in HPV-infected cells. Furthermore, the findings suggest that different events of the IFN inducible signal cascade seem to be target for HPV-16 E7.