Felis catus papillomavirus type 2 E6 and E7 oncogenes are actively transcribed in feline skin cancer in vivo and display transforming properties in vitro

Feline cutaneous squamous cell carcinomas (SCCs) are common skin lesions in cats, mostly arising in old white-coated animals in sun-exposed sites. Recently, an association of these tumours with DNA of Felis catus papillomavirus type 2 (FcaPV2) has been reported, suggesting a role for this virus in the development of SCCs. FcaPV2 potentially encodes for E6 and E7 proteins, which are considered putative oncogenes for analogy with other oncogenic papillomaviruses (PVs). We showed for the first time the expression of viral genes E6, E7 and E2 in vivo in tumour samples and we established the first in vitro model in order to characterize the transforming properties of FcaPV2 E6 and E7 putative oncogenes. The p53 and pRb pathways classically corrupted in PV-induced cancer were found to be impaired by E6 and E7, respectively, and new possible cross-acting mechanisms on the reciprocal pathway were identified. Furthermore, the two oncogenes were able to impair UVB-induced cell cycle arrest and apoptosis, leading to the hypothesis of sun exposure as a co-factor in viral-triggered skin carcinogenesis in the domestic cat, and to prolong the life-span of primary keratinocytes, confirming definitively the transforming properties of FcaPV2. In summary, our study demonstrates for the first time a possible causative role of FcaPV2 in the development of feline skin cancer.