Evidence of a novel cross-species transmission by ovine papillomaviruses

Ovine papillomavirus (OaPV) comprises four genotypes; OaPV1, OaPV2, and OaPV4 are fibropapillomaviruses within the genus Delta -papillomavirus ( Delta- PV ) , whereas OaPV3 is an epitheliotropic virus that belongs to the genus Dyokappa -papillomavirus ( Dyokappa- PV ) . To date, all of them have been known to infect sheep only. OaPV1, OaPV2, and OaPV4 have been associated with ovine cutaneous and mucosal fibropapillomas, while OaPV3 is a key factor in the squamous cell carcinoma (SCC) pathway of the sheep skin. Peripheral blood mononuclear cell (PBMC) samples obtained from 128 cattle at public slaughterhouses were investigated using droplet digital polymerase chain reaction (ddPCR). ddPCR is a new-generation PCR technique that enables accurate and absolute quantification of target molecules with high sensitivity and specificity. All OaPVs were detected by identification and quantification of nucleic acids using specific fluorescent probes. Of 128 PBMC samples, 100 (~78%) showed OaPV infections. Further, 42, 35, and 23 PBMC samples showed single, double, and triple OaPV infections, respectively. OaPV1 was responsible for 22 single infections, OaPV2 caused 16 single infections, and OaPV3 and OaPV4 caused two single infections each. OaPV1 and OaPV2 were the most frequent ovine viruses in dual and triple infections. In many PBMC samples, both ovine Delta- PV and Dyokappa -PV were found to be transcriptionally active, as shown by the detection and quantification of E5 oncogene transcripts for OaPV1, L1 transcripts for OaPV2, E6 and E7 transcripts for OaPV3, and E6 for OaPV4. OaPVs were found in the blood samples from cattle that shared grasslands rich in bracken ferns known to contain immunosuppressant substances. Furthermore, OaPVs were also found in cattle from intensive livestock farming without any contact with sheep. Because OaPV DNA was detected in both grass hay and corn silage, it is conceivable that these feed may be the viral sources.