Genetic Determinants Of Adaption To Rabbits Of C-strain, A Lapinized Attenuated Vaccine Against Classical Swine Fever

Classical swine fever (CSF) is a devastating disease of swine caused by classical swine fever virus(CSFV). The prevention and control of CSF is listed in the National Long-term Animal DiseasePrevention Plan of China (2012-2020). C-strain or HCLV strain, a modified live vaccine against CSF,was developed in China in the mid-1950s after hundreds of passage of a highly virulent CSFV in rabbits.Its sequence was slightly different from highly virulent strains.To identify genetic determinants of adaption to rabbits of C-strain, a series of chimeric virusesbased on C-strain and the highly virulent Shimen strain were generated and evaluated. The chimericvirus vSM-HCLV5NCR containing5-terminal non-coding region (5-NCR) of C-strain showed similargrowth to Shimen strain in SK-6cells. All the other mutants with substitution of partial sequences fromC-strain in the Shimen backbone were shown to be attenuated for in vitro growth compared withShimen strain. Only the chimera vHCLV-SM5NCR containing almost the whole genome but5-NCR ofC-strain grew less vigorously than C-strain.Then all the chimeric viruses were evaluated in rabbits to define the genetic determinants of rabbitfever response. Unexpectedly, all chimeraic viruses did not induce fever in rabbits, even the chimericvirus vHCLV-SM5NCR, which contains almost all genomic sequence except only9-nt difference fromC-strain in the5-NCR. The chimeric viruses vHCLV-SMNCR, vHCLV-SM3NCR andvHCLV-SM5NCR harboring all the coding region of C-strain in the Shimen backbone retained thespleen replication ability of C-strain. The results demonstrated that the entire coding region of C-strainconfers its adaption to rabbits and the complete genome of C-strain, but none of partial fragments,endows to its fever response in rabbits. However, the mechnism why vHCLV-SMNCR,vHCLV-SM3NCR and vHCLV-SM5NCR replicated in the spleen but did not lead to rabbit feverresponse needs to be further investigated.