Oncogenic Potential of Ovine Herpesvirus 2 and Its Molecular Homology with Epstein–Barr Virus

Abstract

Ovine herpesvirus 2 (OvHV-2) causes malignant catarrhal fever (MCF), a lymphoproliferative disease that is often fatal and economically important in cattle and many other susceptible artiodactyls. However, its ability to cause cancer, and its relationship to Epstein-Barr virus (EBV), the classic human tumour gammaherpesvirus, is still unclear. In this study, we combined a critical review of the molecular biology of both viruses with new findings from an Egyptian OvHV-2 isolate to test whether OvHV-2 shares the tumour-forming architecture of EBV. Tongue-mucosa supernatant from a confirmed Egyptian MCF case, previously characterised by complete glycoprotein B (gB) gene sequencing, was examined by negative-staining transmission electron microscopy (TEM) and grown in specific pathogen-free embryonated chicken eggs through the chorioallantoic membrane (CAM) route. TEM showed morphology typical of Burkitt's lymphoma, and CAM growth produced distinct tumours, indicating that OvHV-2 can transform cells even in a non-mammalian host. The comparison showed broad homology between the two viruses, including conserved viral BCL-2, interleukin-10 and BILF1 G-protein-coupled-receptor homologues. The OvHV-2 gB sequence was 99-100% identical to reference genomes and remained stable after passage in cell lines. These results suggest that OvHV-2 is the veterinary equivalent of EBV, with cross-species and possibly zoonotic importance, and raise the possibility that the two are the same virus. We recommend electron microscopy supported by gB sequencing as a rapid first-line diagnostic, and urge screening of cell cultures and a wide range of hosts. For control, we propose OvHV-2 gB subunit vaccination and anti-gB camelid nanobody treatments, and the removal of animal-origin additives from animal feed.