The genetic diversity that occurs among isolates of BVDV is characteristic of RNA viruses that exist in nature as quasispecies
(a swarm of viral mutants). The genetic diversity that occurs among BVDV isolates is reflected in the antigenic diversity
found among viral isolates worldwide. The persistently infected animal is considered important for maintaining BVDV in nature
and as being a primary source of virus for other cattle. Persistently infected cattle may also serves as a source of viral
genetic variants that may be "selected" by non-persistently infected cattle when infected with virus. The emergence and establishment
of genetic and antigenic variants of BVDV also is affected by selective pressure applied to the virus by the innate and adaptive
host immune responses. The array of disease manifestations seen during infection with BVDV, and the corresponding pathogenic
processes, may be attributed to viral diversity; however, the definitive viral markers for tissue tropism or virulence have
yet to be identified.
Basis for Diversity - BVDV the Quasispecies
Studies have shown that BVDV exists as a quasispecies. The ability to mutate rapidly allows BVDV to quickly produce mutants
that are better fit to replicate in the host. Populations of genetic variants of BVDV also have been identified within individual
persistently infected cattle. The detection of genetic variants in persistently infected cattle suggests that those animals
may enhance the diversity of BVDV by serving as a source of viral variants that can infect other cattle.
While there is a tendency to maintain the master nucleic acid sequence of a virus under neutral conditions, the immune response
of the infected host creates a non-neutral condition and may select viral variants. This has been seen on farms that harbor
multiple persistently infected cattle, which likely originated from a single outbreak of acute infection in immunocompetent
pregnant cattle. Comparison of the BVDV from those animals showed that the viral isolates were similar; however, antigenic
differences could be detected among the viral isolates. The selection of the antigenic variants likely occurred during the
acute infection of the dams of those persistently infected cattle and resulted in transplacental transmission slightly different
BVDV to a group of fetuses.
Genetic and Antigenic Diversity
Viral genotypes and genetic diversity – The high frequency of mutation, propensity for recombination, and selective pressure from immune responses stimulated by
natural infection or vaccination has led to the creation of a large assortment of BVDV genetic and antigenic variants. The
genetic variants can be grouped based on the homology of aligned nucleic acid sequences from various segments of the viral
genome. The array of BVDV form genotypes, subgenotypes within genotypes, and isolates within subgenotypes. Pestiviruses segregate
into at least five (possibly six) viral genotypes. Those genotypes are classical swine fever virus, bovine viral diarrhea
virus type 1, bovine viral diarrhea virus type 2, border disease virus, and a genotype represented by a single viral isolate
termed Giraffe-1.
The viral genotypes are about 60% similar to each other in their base sequence. Subgenotypes within a genotype are designated
by a number followed by a lower case letter (BVDV type1a, 1b, etc). Subgenotypes are about 80 to 85% similar to each other.
Currently, 11 subgenotypes of BVDV type 1 and two subgenotypes of BVDV type 2 have been identified. Recent phylogenetic surveys
suggest that there are regional differences in the distribution of viral genotypes and subgenotypes. The regional distribution
of viral genotypes and subgenotypes likely reflects historical routes for movement of cattle, vaccine usage over time, and
geographic isolation of cattle populations. There is some linkage of viral genotypes and subgenotypes with clinical manifestations
of disease including thrombocytopenia, reproductive failure, or pneumonia.
Antigenic diversity – The genetic diversity seen among BVDV results in extensive antigenic diversity. Most field isolates of BVDV show unique patterns
of monoclonal antibody binding when reacted with a large panel of monoclonal antibodies raised against several different viruses.
In fact, BVDV isolates that are antigenically alike in monoclonal antibody assays are difficult to find.
Viruses are readily segregated into genotypes by patterns of monoclonal antibody binding. Similarly, segregation of BVDV into
genotypes can be done using convalescent serum or post vaccinal serum in viral neutralization assays. Antigenic differences
likely exist between subgenotypes, but the diverse antibody response that occurs among cattle after infection or vaccination
makes it difficult to consistently separate viruses into subgenotypes using polyclonal antibody. In summary, BVDV exists as
an antigenically diverse array of viruses that manage to retain some antigenic similarity with each other and with other pestiviruses.
