Submitted to: Ruminant Pestiviruses Symposium Proceedings
Publication Type: Proceedings
Publication Acceptance Date: September 13, 2005
Publication Date: September 13, 2005
Citation: Ridpath, J.F. 2005. Pestivirus evolution, vaccines and diagnostics. In: Proceedings of the 6th Pestiviruses Symposium, September 13-16, 2005, Thun, Switzerland. p. 18. Technical Abstract: There are several factors that differentiate the pestivirus genus from other members of the flavivirus family. Among these are the production of the nonstructural protein, N**pro and antigenic cross reactivity. Sequence comparison of N**pro coding regions reveals seven major phylogenetic branches within the pestivirus genus. Four of these branches correspond to the four recognized species of pestivirus; bovine viral diarrhea virus 1 (BVDV1), BVDV2, border disease virus (BDV) and classical swine fever virus (CSFV). The three remaining branches include a branch made up of a pestivirus isolated from giraffe, one branch composed of a pestivirus isolated from a pronghorn antelope and one branch consisting of three pestiviruses, one isolated from Brazilian fetal calf serum, one isolated as a contaminant from cultured cells and one isolated from a Brazilian buffalo. Phylogenetic analysis indicates that "novel" viruses isolated from Chamois sheep, reindeer and pig belong to the BDV branch. Similarly an isolate from Tunisian sheep can be grouped in the CSFV branch. Sequence identity between branches ranges from 68% to 61% with the exception of the pronghorn branch which has a sequence identity of 47% to the other branches. Sequence divergence is higher among viruses within the BDV and CSFV branches. While all pestiviruses are antigenically cross reactive, viruses characterized to date demonstrate a higher antigenic similarity with viruses segregated to the same phylogenetic branch than viruses from different phylogenetic branches. Vaccines are widely available against BVDV1, BVDV2 and CSFV. Neutralizing epitopes are found on the E2 protein of all pestiviruses characterized to date. In addition, neutralizing epitopes have been reported on the E**rns protein of CSFV. Protection accorded by subunit and killed vaccines have correlated to the development of serum antibodies against the E2 protein. Research suggests that the T cell response is as important, if not more important, as the B cell response in the development of acquired immunity against pestiviruses. However, research on T cell responses has been limited by the lack of simple, robust and reliable methods for measuring and comparing T cell responses. The focus of vaccination against CSFV has been the reduction of clinical disease and viral shed following acute infection. In addition to controlling acute disease there is a desire for BVDV1 and BVDV2 vaccines to limit fetal infections that result in the generation of persistently infected animals. Providing fetal protection is proving to be a much more stringent requirement than reduction of clinical disease. As eradication programs progress there will be an increased need for coupled vaccines and diagnostics that allow for the differentiation of vaccinated animals from naturally infected animals. Eradication programs and the realization that pestivirus infections can not be diagnosed based on the "classic" clinical presentation of disease has led to an increased emphasis on development of diagnostics. Similar to vaccines, most of the available diagnostics are geared to the detection of CSFV, BVDV1 and BVDV2. Standard tests for detection of pestiviruses are reliable but there is a push to develop faster "pen side" tests. As some pestiviruses are eradicated there will be a greater need for tests that differentiate between eradicated and endemic pestiviruses. While there are antibody tests that differentiate between some pestiviruses, increasingly differential tests are based on sequence comparison or polymerase chain reaction (PCR) amplification. A number of these tests have been developed based on conserved motifs found within the 5’ noncoding region. CSFV diagnostics are designed to detect acute infections while most diagnostics for BVDV1 and BVDV2 are geared toward detection of persistently infected (PI) animals. Recently there has been a surge in the development of tests using skin biopsies as samples to detect these (PI) animals. The ultimate test would be a "pen side" test with a range broad enough to detect all genotypes of pestiviruses that would at the same time differentiate between the different genotypes and acute and persistent infections.