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The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-β. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo . Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer., Competing Interests: The authors declare no conflict of interest.

Human papillomavirus (HPV) is a DNA virus that infects epithelial cells and has been implicated in the development of cervical cancer. Few therapeutic strategies have been designed for the treatment of cervical intraepithelial neoplasia, a precursor of cervical cancer. In these early stages, the HPV E2 protein is the most important viral factor involved in viral gene expression and plays crucial roles during the vegetative viral cycle in epithelial cells. Papillomavirus E2 binds specifically to palindromic ACCN 6 GGT sequences, referred to as the E2 binding sites (E2BS), which are concentrated within the viral long control region, and which are responsible for regulation of the HPV protein's expression. Here, we consider E2BS as a candidate sequence to induce the expression of antiviral therapeutic genes selectively in HPV-infected cells expressing the E2 protein. This study focuses on the use of an HPV-specific promoter comprised of four E2BS to drive the expression of IL-12, leading to an antitumor effect in an HPV-positive murine tumor model. The therapeutic strategy was implemented via viral gene therapy using adenoviral vectors with recombinant E2 and IL-12 genes and E2BS-IL-12. We demonstrate that the HPV-specific promoter E2BS is functional in vitro and in vivo through transactivation of HPV E2 transcription factor., Competing Interests: The authors declare no conflict of interest.