The origin of the cytopathogenic BVDV has been a controversial issue but there is grow evidence that it arises from a mutational change from the persisting BVDVnc. The manner of this mutation is complex and still an active area of research.

There can, however, be little doubt that it can arise de novo from BVDVnc: as a consequence, any animal that is PI can, even in isolation, develop mucosal disease ( see below).