Bovine viral diarrhea virus (BVDV) is a pathogen of cattle that is found worldwide. It is one of the three recognized viral species making up the pestivirus genus. The other two members of the pestivirus genus, border disease of sheep and hog cholera virus, are serologically related to BVDV.

Infection with BVDV results in a variety of diseases ranging from subclinical to highly fatal. Many BVDV viruses cause only clinically inapparent or mild disease in nonpregnant adult cattle. However, when pregnant animals become infected these same viruses can cause congenital malformations and/or fetal death. In addition, highly virulent strains of BVDV have emerged that are capable of inducing severe disease during acute uncomplicated primary infections.

BVDV may exist as one of two biotypes, cytopathic or noncytopathic. In cattle the two biotypes differ in that noncytopathic, but not cytopathic BVDV, may establish life long persistent infections. An animal that is persistently infected with noncytopathic BVDV may become superinfected with a cytopathic BVDV. The two viruses may then interact to cause mucosal disease, which is highly fatal.

Antigenic variation among BVDV has been detected using convalescent antiserum from cattle and monoclonal antibodies from mice. This antigenic variation among BVDV has caused problems with antibody-based diagnostic reagents. Further, antigenic variation among viruses may contribute to vaccine failure.

Recently BVDV have been segregated into two genotypes. Originally these two genotypes were called BVDV type I and BVDV type II. In keeping with the conventions used in categorizing other viruses, they are now referred to as BVDV 1 and BVDV 2. The recognition of a second genotype of BVDV has resulted in much discussion among cattle producers and the manufacturers of veterinary biologics. Genotyping is merely a way of categorizing BVDV. Viruses with different genotypes belong to different branches of an evolutionary tree. Because the genome of BVDV consists of a single-stranded molecule of RNA, the virus has an inherent tendency to vary at the genomic level. Unlike double-stranded DNA genomes, there is no proofreading function associated with replicating a single-stranded RNA genome. Therefore, errors introduced in making the virus, which do not interfere with the functions, are maintained. However, even considering this inherent variability, the genomes of BVDV 1 viruses are very different from the genomes of BVDV 2 viruses.

Because it is prohibitive to sequence the entire genome of a BVDV to decide its genotype, segregation of BVDV into the BVDV 1 or BVDV 2 genotype is based on comparison of the portion of the genome that has the least variability, the 5' untranslated region. Changes rarely occur in this region and those changes that do occur tend to be stable.

Thus, BVDV may vary by virulence, biotype, antigenicity, and genotype. Currently there is no scientific connection between virulence, biotype, antigenicity, and genotype. That is, two viruses may belong to different biotypes but have the same antigenic profile. Similarly, two viruses may belong to the same biotype but have different genotypes or belong to the same genotype but differ in virulence.

That said, viruses from the two genotypes are antigenically distinct. (Please note that this is different from saying that all viruses within a genotype are antigenically the same.) Several BVDV 2 viruses have been isolated from persistently infected animals born to dams that had been vaccinated with a BVDV 1 virus. This raises the question of whether antibodies raised against a virus from one genotype will offer protection against infection with a virus belonging to the other genotype. Studies are now underway in our laboratory to examine cross-protection between BVDV 1 and BVDV 2 and evaluate the efficacy of vaccines containing both BVDV 1 and BVDV 2. Because these studies are not yet complete we cannot define what significance genotype has in vaccine development and control of BVDV. Further, we do not yet know how serologically broad the differences are within either BVDV genotype.

Genotype should not be confused with virulence. While viruses associated with recent outbreaks of hemorrhagic syndrome and peracute BVD belong to the BVDV 2 genotype, not all BVDV 2 viruses are virulent. There are BVDV 2 viruses that are avirulent, just as there are BVDV 1 viruses that have killed animals. Further studies will be necessary to determine the factors responsible for virulence of these viruses.