Bovine Papillomavirus Type 1 in Brains of Cattle with a Neurological Syndrome: Pathological and Molecular Study

Bovine papillomavirus (BPV) infection is endemic in Brazilian herds. Papillomaviruses are oncogenic, with a trophic response in squamous epithelial and mucosal tissues, and are associated with asymptomatic infections, proliferative benign skin lesions (papillomas), and malignant epithelial lesions (carcinomas). The presence and expression of BPV in the blood of healthy and papillomatosis-affected cattle has been demonstrated. Experimental inoculation of Bovine papillomavirus (BPV) into calf meninges can result in meningiomas and papillomatosis, but it´s not known if its natural infection causes neoplasia and neurological syndrome in cattle. We assessed the frequency of BPV in 300 Central Nervous System (CNS) samples from cattle with neurological syndrome from several Brazilian regions obtained from surveillance of neurological syndrome. Samples were negative for rabies, Neospora caninum, BoHV-1 and BoHV-5, bovine leukemia virus, and catarrhal malignant fever (PCR). Samples were fixed in 10% buffered formalin and submitted to macroscopic examination. For histological analysis, slides were submitted to a staining protocol using hematoxylin and eosin. PCR for BPV detection was applied in CNS frozen samples using generic primers FAP59 and FAP64 (L1 gene). Thirteen (4.3%) samples were positive for BPV by PCR, with 11 of these showing no pathological changes in microscopy, and two exhibiting nonspecific non-purulent meningoencephalitis. No CNS samples showed neoplasia. Nine of the 13 BPV positive samples (69.2%) came from females and four (30.8%) from males. The 13 positive animals were age 5 to 168 months with seven over 36 months (53.8%). Five were dairy cattle, four crossbred, and three beef cattle. Only one of the 13 positive samples provided sufficient BPV DNA for sequencing, which emonstrated 99% identity to samples of BPV-1 obtained from cutaneous papillomas in cattle in Brazil. The small quantity of BPV DNA in the CNS and the low number of PCR-positive samples may be associated with low neurotropism, unspecific inflammation, or BPV-infected lymphocytes in CNS tissues or bloodstream. Natural BPV-1 infection was not associated with cerebral neoplasia or neurological syndrome.