Complete canine papillomavirus life cycle in pigmented lesions

Canine papillomaviruses (CPVs) have been identified in various benign and malignant neoplastic skin disorders. The most frequent manifestations of CPV infections are classical warts and pigmented plaques. Although the etiology of canine oral papillomatosis is well established, knowledge about CPVs role in the development of pigmented plaques remains vague. Indeed, as CPV DNA may frequently be found on clinically healthy canine skin, its mere detection in lesions cannot be regarded as a sufficient indicator of causality. Whether CPVs are actually active in pigmented plaques, a requirement for any conceivable involvement, is consequently an open question. To inquire such viral activity, two distinct clinical cases of canine pigmented lesions were evaluated in greater detail. The histological findings in the two cases supported the clinical diagnosis of pigmented viral plaques. Sequencing of amplified DNA from these lesions revealed the genomes of two novel CPV types, i.e. CPV9 and CPV14, both putatively belonging to the genus Chi. Furthermore, transcription and splicing of corresponding CPV mRNA could be shown by RT-PCR in the respective lesions. Finally, viral particles were detected by electron microscopy in homogenates as well as in nuclei of keratinocytes in pigmented lesions. In conclusion, the results link clinical signs of pigmented plaques to histological changes, the presence of CPV specific DNA, viral gene transcription, and the presence of viral particles in and from the lesions. Thus, the findings outline the entire replicative cycle of CPVs in pigmented plaques, which might help understanding the relationship between these viruses and the associated disorders.