Bovine respiratory syncytial virus lacking the virokinin or with a mutation in furin cleavage site RA(R/K)R109 induces less pulmonary inflammation without impeding the induction of protective immunity in calves

J Gen Virol. 2006 Jun;87(Pt 6):1659-67. doi: 10.1099/vir.0.81755-0.

Abstract

The BRSV fusion (F) protein is cleaved at two furin consensus sequence sites, resulting in the generation of disulphide-linked F1 and F2 subunits and the release of an intervening peptide of 27 amino acids (pep27), which is converted into a biologically active tachykinin (virokinin). The role of the virokinin and the importance of one of the furin cleavage sites, FCS-2 [RA(R/K)R109], in the pathogenesis of BRSV infection and in the subsequent development of immunity was studied in gnotobiotic calves infected with a recombinant BRSV (rBRSV) lacking pep27 (rBRSVdelta p27) or with rBRSV108/109, which contains two amino acid substitutions in FCS-2 (RANN109). Although replication of the mutant viruses and the parental wild-type (WT) rBRSV in the lungs was similar, the extent of gross and microscopic lesions induced by the mutant viruses was less than that induced by WT rBRSV. Furthermore, the numbers of eosinophils in the lungs of calves infected with the mutant viruses were significantly less than that in calves infected with WT virus. These observations suggest a role for the virokinin in the pathogenesis of BRSV infection. Following mucosal immunization with rBRSVdelta p27, the levels of BRSV-specific serum antibodies were similar to those induced by WT virus. In contrast, the level of neutralizing antibodies induced by rBRSV108/109 was 10-fold lower than that induced by WT virus. Nevertheless, resistance to BRSV challenge induced by the mutant and WT viruses was similar, suggesting that neither pep27 nor FCS-2 plays a major role in the induction of protective immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cattle Diseases / immunology*
  • Cattle Diseases / virology
  • Cells, Cultured
  • Furin / metabolism
  • Germ-Free Life
  • Immunization
  • Molecular Sequence Data
  • Mutation*
  • Pneumonia / immunology
  • Pneumonia / physiopathology
  • Pneumonia / veterinary*
  • Recombination, Genetic
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / veterinary*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus Vaccines / administration & dosage*
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology
  • Respiratory Syncytial Virus, Bovine / genetics
  • Respiratory Syncytial Virus, Bovine / immunology
  • Respiratory Syncytial Virus, Bovine / pathogenicity*
  • Tachykinins / metabolism
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / genetics*
  • Viral Fusion Proteins / metabolism
  • Virulence

Substances

  • Respiratory Syncytial Virus Vaccines
  • Tachykinins
  • Viral Fusion Proteins
  • Furin