The role of noncoding regions of classical swine fever virus C-strain in its adaptation to the rabbit

•We rescued a series of chimeras derived from C-strain and Shimen strain.•Rabbits inoculated with any of the chimeras developed antibodies but not fever.•The NCRs of C-strain are essential for its fever induction in rabbits.•Chimeras harboring the entire coding region of C-strain replicated in the spleen of rabbits.•The NCRs of C-strain are not necessary for its replication in the spleen of rabbits.

Classical swine fever (CSF) is a devastating disease of swine caused by classical swine fever virus (CSFV). C-strain, a modified live vaccine against CSF, was developed through hundreds of passages of a highly virulent CSFV in the rabbit in China in the mid-1950s. To identify the role of noncoding regions (NCRs) of C-strain in its adaptation to the rabbit, we generated and evaluated a series of chimeric viruses derived from C-strain and the highly virulent Shimen strain. The results demonstrated that the NCRs of the C-strain were essential for its fever induction in rabbits and the coding region but not NCRs was necessary for its replication in the spleen of rabbits.