Basic science paves the way to novel safe and effective pestivirus vaccines

Abstract Pestiviruses are among the economically most important pathogens of livestock. Except for culling, vaccination represents the only feasible way to control pestiviruses. Therefore, a considerable number of pestivirus vaccines have been developed and put on the market. However, these vaccines still have disadvantages that should be eliminated in future approaches, some of which are based on recent findings and will be outlined in this chapter. One of the most important features of ruminant pestiviruses is their extraordinary tendency to establish lifelong persistence as the outcome of intrauterine infection. As a result, 1-2% of cattle worldwide are persistently infected with bovine viral diarrhea virus. The constant dissemination of the virus by these animals is central for maintenance of this pathogen in its host population; therefore, future vaccines must address this highly relevant problem. Elucidation of the molecular features of pestiviruses that are required for the establishment and maintenance of persistent infection has made significant progress, and the present knowledge on this topic is summarized in this chapter. These features include a unique strategy to restrict virus genome replication by a limiting host factor and viral virulence factors N^pro and E^rns interfering with the innate immune response of the host. Accordingly, a framework of viral functions is involved in the establishment and maintenance of persistence. On the basis of this knowledge, specific mutations in the recently identified virulence factors have resulted in the generation of attenuated viruses, building a perfect basis for future vaccine design.