Identification of a Novel Papillomavirus Associated with Squamous Cell Carcinoma in a Domestic Cat

Abstract

Papillomaviruses infect the skin and mucosal surfaces of diverse animal hosts with consequences ranging from asymptomatic colonization to highly malignant epithelial cancers. Increasing evidence suggests a role for papillomaviruses in the most common cutaneous malignancy of domestic cats, squamous cell carcinoma (SCC). Using total DNA sequencing we identified a novel feline papillomavirus in a nasal biopsy taken from a cat presenting with both nasal cavity lymphoma and recurrent squamous cell carcinoma affecting the nasal planum. We designate this novel virus as Felis catus papillomavirus 6 (FcaPV6). The complete FcaPV6 7453 bp genome was similar to those of other feline papillomaviruses and phylogenetic analysis revealed that it was most closely related to FcaPV3, although was distinct enough to represent a new viral type. Classification of FcaPV6 in a new genus alongside FcaPVs 3, 4 and 5 is supported. Archived excisional biopsy of the SCC, taken 20 months prior to presentation, was intensely positive on p16 immunostaining. FcaPV6, amplified using virus-specific, but not consensus, PCR, was the only papillomavirus detected in DNA extracted from the SCC. Conversely, renal lymphoma, sampled at necropsy two months after presentation, tested negative on FcaPV6-specific PCR. In sum, using metagenomics we demonstrate the presence of a novel feline papillomavirus in association with cutaneous squamous cell carcinoma.

Papillomaviruses in Domestic Cats

“…The most recent PV type to be fully sequenced from domestic cats was also detected in a skin lesion and was reported in 2020 [ 61 ]. The L1 ORF sequence of this PV type is most similar to FcaPV3 suggesting that this PV will also be classified as a species 3 Taupapillomavirus .…”

Comparison of prevalence of <i>Felis catus</i> papillomavirus type 2 in squamous cell carcinomas in cats between Taiwan and Japan

“…As one of the causative agents in feline SCC development, Felis catus papillomavirus (FcaPV) infection has been suggested [22,24]. To date, six genotypes of FcaPVs have been detected and characterized from cutaneous/mucosal lesions in cats [8]. Among the six FcaPV types, FcaPV type 2 (FcaPV2) has been commonly identified in SCCs from the studies in Europe [2], Oceania [21,29], and North America [26].…”

Discovery and Characterization of Actively Replicating DNA and Retro-Transcribing Viruses in Lower Vertebrate Hosts Based on RNA Sequencing

“…These methods provide an unbiased view of the virome within a host, expand our knowledge of viral diversity, and fill in the "gaps" between many higher virus taxa [1][2][3][4]. Among various metagenomic methods used for virus discovery, metatranscriptomics (i.e., total RNA sequencing) represents a simple but efficient approach that not only transforms our view of the genomic diversity of RNA viruses in a wide range of hosts [5][6][7], but also expands our knowledge of the diversity of DNA viruses [8][9][10][11]. Indeed, after reanalyzing the 92 metatranscriptomics data from invertebrate RNA sequencing, Porter et al [9] were able to reveal DNA viruses from at least 29 families, including 19 novel species from both large and small DNA virus families, and with good genome coverage.…”

“…Furthermore, with RNA sequencing, some DNA viruses can reach extremely high abundance levels [8], reflecting active RNA transcription and potentially acute infection within the host. On the other hand, metatranscriptomics can also reveal genomic information from viruses that are often known for chronic and latent infections, such as herpesviruses and papillomaviruses [10,11], which highlights the capacity of RNA sequencing for the discovery of viruses other than those with RNA genomes.…”