Table 2.

IFN immune activities and HPV interferences.

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