IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression.
The effects of interferon-tau (IFN-tau) on tumor suppressor factors and virus oncoprotein expression were compared with two other type I IFN in human papillomavirus (HPV-16)-transformed cells. Nontumorigenic human keratinocytes, HuKc/HPV-16d-2C (d-2C), treated with recombinant human IFN-alpha2a (Roferon), a human recombinant alpha IFN hybrid, alpha B/D (IFN-alphaB/D), or ovine IFN-tau were evaluated for their effects on the levels of E6 and E7 expression. IFN-tau was comparable to IFN-alpha2a in decreasing intracellular levels of E6 and E7, and IFN-alphaB/D was more effective than IFN-a2a in suppressing E7 levels. All three IFN were capable of increasing the cellular concentration of wild-type p53 tumor suppressor with the magnitude IFN-tau > IFN-alpha2a > IFN-alphaB/D. Increases in p53 concentrations correlated with the observed decreases in E6 mRNA and protein levels. The antiviral effects observed in this study reveal that IFN-tau has potent antipapillomavirus activity. Sequences/structures unique to IFN-tau could allow for alternative IFN/receptor interactions and may explain the differences in biologic function.
Johnson
J A
JA
Department of Microbiology, Greenville Hospital System/Clemson University Biomedical Cooperative, Clemson, SC 29634, USA. jlj6@cdc.gov
Hochkeppel
H K
HK
Gangemi
J D
JD
D000998:Antiviral Agents / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D003864:Depression, Chemical; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D011257:Pregnancy Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000998:Antiviral Agents; C068651:E6 protein, Human papillomavirus type 16; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C020947:interferon tau; C059731:oncogene protein E7, Human papillomavirus type 16