Recombinant bovine respiratory syncytial virus with deletion of the SH gene induces increased apoptosis and pro-inflammatory cytokines in vitro, and is attenuated and induces protective immunity in calves.

Bovine respiratory syncytial virus (BRSV) causes inflammation and obstruction of the small airways, leading to severe respiratory disease in young calves. The virus is closely related to human (H)RSV, a major cause of bronchiolitis and pneumonia in young children. The ability to manipulate the genome of RSV has provided opportunities for the development of stable, live attenuated RSV vaccines.

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.

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.

DNA vaccination against respiratory syncytial virus in young calves.

A DNA vaccine encoding the fusion (F) gene (DNA-F) of bovine respiratory syncytial virus (BRSV) induced significant protection against BRSV infection in young calves. However, serum antibody to RSV developed more slowly in animals vaccinated with DNA-F when compared with those previously infected with BRSV. Furthermore, protection against BRSV infection was not as great as that induced by prior BRSV infection.

Role of alpha/beta interferons in the attenuation and immunogenicity of recombinant bovine respiratory syncytial viruses lacking NS proteins.

Alpha/beta interferons (IFN-alpha/beta) are not only a powerful first line of defense against pathogens but also have potent immunomodulatory activities. Many viruses have developed mechanisms of subverting the IFN system to enhance their virulence. Previous studies have demonstrated that the nonstructural (NS) genes of bovine respiratory syncytial virus (BRSV) counteract the antiviral effects of IFN-alpha/beta.

Resistance to bovine respiratory syncytial virus (BRSV) induced in calves by a recombinant bovine herpesvirus-1 expressing the attachment glycoprotein of BRSV.

The ability of a bovine herpesvirus-1 (BHV-1) recombinant expressing the G protein of bovine respiratory syncytial virus (BRSV) to protect against BRSV infection was examined in calves. A synthetic G gene was inserted behind the gE promoter of BHV-1 to give a gE-negative, BHV-1/G recombinant. Gnotobiotic calves, vaccinated intranasally and intratracheally with BHV-1/G were challenged 6 weeks later with the Snook strain of BRSV.