Congenital papillomavirus infection in cattle: Evidence for transplacental transmission.

Vertical transmission of bovine papillomavirus (BPV) infection was investigated on livers and kidneys of four foetuses from cows suffering from BPV-2-associated urothelial cancers of the urinary bladder. PCR analysis revealed the presence of BPV-2 E5 DNA in the livers and kidneys of two foetuses. Amplified DNA fragments, composed of 502 bp, showed a 100% homology with BPV-2 sequences (GenBank accession number: M20219.1). BPV-2 was found to be transcriptionally active. Indeed, reverse transcriptase (RT)-PCR showed BPV-2 E5 transcripts. Sequencing of amplified cDNA, composed of 154 bp, showed a 100% identity with BPV-2 E5 sequences (GenBank accession number: M20219.1). Western blot analysis revealed the presence of dimers of E5 oncoprotein. Furthermore, a statistically significant increase of the phosphorylated (activated) form of the platelet-derived growth factor ß receptor (PDGFßR) was also detected in the fetal tissues. PDGFßR is believed to form the most important interaction with the E5 oncoprotein, thus regulating biological activity of virus protein. The strong concordance between virus found in fetal organs with virus detected in infected mothers provides evidence that BPV-2 can spread through blood and vertical infection occurs via transplacental transmission. Finally, molecular findings of this study raise unsolved questions about the potential role of BPVs in reproductive disorders. The presence of E5 oncoprotein, as in adult organs, may also activate the constitutive receptor PDGFßR in foetal organs, which plays a pivotal role in angiogenesis and embryonic development. Therefore, abnormal phosphorylation of PDGFßR may be involved in vascular and organogenesis abnormalities other than cancer.