IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression

The effects of interferon-tau (IFN-tau) on tumor suppressor factors and vir us oncoprotein expression were compared with two other type I IFN in human papillomavirus (HPV-16)-transformed cells. Nontumorigenic human keratinocyt es, HuKc/HPV-16d-2C (d-2C), treated,vith recombinant human IFN-alpha 2a (Ro feron), a human recombinant alpha IFN hybrid, alpha B/D (IFN-alpha B/D), or ovine IFN-tau were evaluated for their effects on the levels of E6 and E7 expression. IFN-tau was comparable to IFN-alpha 2a in decreasing intracellu lar levels of E6 and E7, and IFN-alpha B/D was more effective than IFN-alph a 2a in suppressing E7 levels, All three IFN were capable of increasing the cellular concentration of wild-type p53 tumor suppressor with the magnitud e IFN-tau > IFN-alpha 2a > IFN-alpha B/D. Increases in p53 concentrations c orrelated with the observed decreases in E6 mRNA and protein levels. The an tiviral effects observed in this study reveal that IFN-tau has potent antip apillomavirus activity. Sequences/structure unique to IFN-tau could allow f or alternative IFN/receptor interactions and may explain the differences in biologic function.