IFN-I (IFN-α/β) |
Activities
|
IFN-α inhibits keratinocyte immortalization induced by HPV16 [53] |
Boosts IFN-γ secretion [54] and Th1 response [55] |
Induces antibody production [54] |
Induces resistance to viral replication [56] |
Induces MHC class I and II expression [54] |
Induces the activation of NK cells [56] |
Plays antiangiogenic and antiproliferative activities [57] |
Induces DC maturation and T cell proliferation and priming [54] |
Turns virus-infected cells more susceptible for CTL killing [56] |
Alters the B cell isotype and differentiation into plasma cell [54] |
Prevents T cell apoptosis [54] |
Promotes the proliferation of memory T cells [54] |
HPV interferences
|
Its signal transduction pathways are prevented by E6 and E7 activities [18] |
IFN-α signalling is inhibited by (i) HPV18 E6 interaction with Tyk2 (tyrosine kinase 2), (ii) E6 binding to IRF-3 which prevents IFN-α transcription, and (iii) HPV16 E7 prevention of the displacement of p48 (subunit of interferon-stimulated gene factor 3 (ISGF3)) to the nucleus |
HPV16 E7 also inhibits IRF-1-mediated IFN-β transcription by physically interacting with IRF-1 |
IFN-α and IFN-β are also downregulated by E6-mediated inhibition of STAT1 binding to ISRE and prevention STAT1 expression [57] |
|
IFN-II (IFN-γ) |
Activities
|
IFN-γ as well as IFN-I inhibit transcription of E6/E7 genes in immortalized keratinocytes and malignant cells [48] |
Upregulates MHC class I in immune and tumor cells [58] as well as MHC I/II in epithelial cells [18] |
Promotes differentiation to the Th1 profile and induces these cells to produce IFN-γ [59] |
Plays antiviral, antiproliferative [58], and tumor cell killing activities, being associated with lesion regression [60] |
Boosts the synthesis of inducible nitric oxide synthase, IP-10 (protein 10 inducible by IFN-γ) and Mig (monocin inducible by IFN-γ) chemokines by macrophages, which augment cytotoxic response [58] |
Induces NK cell infiltration and activation [58] |
Induces TAP-1 (transporter antigen processing-1) and MCP-1 expression, which are important for T cell antigen recognition and chemoattraction, respectively [58] |
HPV interferences
|
The expression of TAP-1 and MCP-1 is prevented by E7 and E6/E7, respectively [48] |
|
IFN-III (IFN-λ) |
Activities
|
Prevents several tumor cell lines growth [61] |
Promotes antiviral and antitumor responses [61] |
In the treatment of viral and neoplastic diseases it has been tested with type I IFNs showing synergic effects and reduced side effects [61] |
HPV interferences
|
None reported |