Bovine viral diarrhea virus: Antigenic diversity and practical consequences (Proceedings)
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.