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Classical swine fever (CSF), a highly contagious disease of pigs caused by the classical swine fever virus (CSFV), can lead to important economic losses in the pig industry. Numerous CSFV isolates with various degrees of virulence have been isolated worldwide, ranging from low virulent strains that do not result in any apparent clinical signs to highly virulent strains that cause a severe peracute hemorrhagic fever with nearly 100% mortality. Knowledge of the molecular determinants of CSFV virulence is an important issue for effective disease control and development of safe and effective marker vaccines. In this review, the latest studies in the field of CSFV virulence are discussed. The topic of virulence is addressed from different angles; nonconventional approaches like codon pair usage and quasispecies are considered. Future research approaches in the field of CSFV virulence are proposed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Classical swine fever virus (CSFV) is a positive-sense RNA virus with a high degree of genetic variability among isolates. High diversity is also found in virulence, with strains covering the complete spectrum from avirulent to highly virulent. The underlying genetic determinants are far from being understood. Since RNA polymerases of RNA viruses lack any proof-reading activity, different genome variations called haplotypes, occur during replication. A set of haplotypes is referred to as a viral quasispecies. Genetic variability can be a fitness advantage through facilitating of a more effective escape from the host immune response. In order to investigate the correlation of quasispecies composition and virulence in vivo, we analyzed next-generation sequencing data of CSFV isolates of varying virulence. Viral samples from pigs infected with the highly virulent isolates "Koslov" and "Brescia" showed higher quasispecies diversity and more nucleotide variability, compared to samples of pigs infected with low and moderately virulent isolates., (Copyright © 2013 Elsevier Inc. All rights reserved.)