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 Protein (GBP)-ISRE reporter activation by IFN-gamma thus suggesting an alteration of the IRF-1 function. In this study we examined the mechanism by which E7 affects the IFN-gamma signals driving the activation of gene transcription. Using 14/2 BRK cells containing dexamethasone-inducible HPV-16 E7 gene, 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 expression. Likewise, in vitro translated E7 did not affect the IRF-1 DNA binding activity in nuclear extracts derived from IFN-induced cells, thus indicating that the effects of E7 are upstream of IRF-1's binding to its DNA recognition site. Finally, NFkappaB DNA binding activity was also inhibited under conditional expression of E7. These data indicate that HPV-16 E7 inhibits the IRF-1 and NFkappaB 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.
Perea
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Division of Cellular Biology, Center for Biological Research, Cubanacan, Havana 6996, Cuba.
Massimi
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Banks
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D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D011994:Recombinant Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D003907:Dexamethasone; D007371:Interferon-gamma