Abstract
Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are suggested as one of the risk factors for the development of squamous cell carcinomas (SCCs). In the present study, the full genomes of two CPV9 strains from recurrent SCCs of Dog 1 and skin viral papilloma (viral plaque) of Dog 2 were sequenced. Alignment of the two CPV9 sequences with the genome of the reference CPV9 strain (accession no. JF800656.1) derived from a solitary pigmented plaque was performed. Compared with the reference strain, a 27 bp in-frame insertion in the E1 gene was identified in both CPV9 strains in this study. In comparison with the CPV9 strains derived from benign lesions, the CPV9 from the SCCs of Dog 1 exhibited a 328 bp deletion at the 3′ end of the E2 and spacer sequence, which encoded a truncated deduced E2 protein and a chimeric E8^E2 protein. However, there was no difference in the mRNA expression levels of viral oncoproteins of E6 and E7 between the two CPV9 cases, suggesting that the oncogenesis of CPV9 for malignant transformation might be different from that of human papillomaviruses. The roles of E2 and E8^E2 deleted CPV9 in the oncogenesis of benign and malignant lesions should be further investigated.
Highlights
Papillomaviruses (PVs) were first identified from cutaneous lesions and linked to human cancer in the nineteenth century [1,2]
Histological Descriptions and Immunohistochemistry Staining In Dog 1, multiple skin masses on the trunk and digits were diagnosed as cutaneous horns and multicentric papillomas covered by hyperpigmented squamous epithelium (Figure 1a)
The inguinal masses from Dog 1 were diagnosed as squamous cell carcinomas (SCC) with the features of moderate keratinization, an obvious deep invasive pattern, moderate nuclear pleomorphism, and a low mitotic rate; it was categorized as grade 2 SCC based on the Invasive Front Grading System (Figure 1b) [35]
Summary
Papillomaviruses (PVs) were first identified from cutaneous lesions and linked to human cancer in the nineteenth century [1,2]. They are small double-strained DNA viruses that can infect various animal species and have strong species and tissue tropism [3]. Papillomavirus infections are usually asymptomatic or cause proliferative cutaneous lesions such as papillomas, pigmented plaques, and warts [3,5]. These benign hyperplastic lesions can be spontaneously eradicated by elevated host innate immunity as well as cell-mediated immunity [6,7,8]. Some specific types of PVs, such as human papillomavirus (HPV) types 16 and 18, have been proven to be ‘high-risk’ oncogenic viruses that cause malignant cutaneous and genital neoplasms in humans [9]
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