-Bovine respiratory syncytial virus (BRSV) belongs to the pneumovirus genus within the family Paramyxoviridae and is a major cause of respiratory disease in young calves. BRSV is enveloped and contains a negative sense, single-stranded RNA genome encoding 11 proteins. The virus replicates predominantly in ciliated respiratory epithelial cells but also in type II pneumocytes. It appears to cause little or no cytopathology in ciliated epithelial cell cultures in vitro, suggesting that much of the pathology is due to the host's response to virus infection. RSV infection induces an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. Although the mechanisms responsible for induction of these chemokines and cytokines are unclear, studies on the closely related human (H)RSV suggest that activation of NF-κB via TLR4 and TLR3 signalling pathways is involved. An understanding of the mechanisms by which BRSV is able to establish infection and induce an inflammatory response has been facilitated by advances in reverse genetics, which have enabled manipulation of the virus genome. These studies have demonstrated an important role for the non-structural proteins in anti-interferon activity, a role for a virokinin, released during proteolytic cleavage of the fusion protein, in the inflammatory response and a role for the SH and the secreted form of the G protein in establishing pulmonary infection. Knowledge gained from these studies has also provided the opportunity to develop safe, stable, live attenuated virus vaccine candidates.

African swine fever (ASF) is an acute haemorrhagic disease of domestic pigs for which there is currently no vaccine. We showed that experimental immunisation of pigs with the non-virulent OURT88/3 genotype I isolate from Portugal followed by the closely related virulent OURT88/1 genotype I isolate could confer protection against challenge with virulent isolates from Africa including the genotype I Benin 97/1 isolate and genotype X Uganda 1965 isolate. This immunisation strategy protected most pigs challenged with either Benin or Uganda from both disease and viraemia. Cross-protection was correlated with the ability of different ASFV isolates to stimulate immune lymphocytes from the OURT88/3 and OURT88/1 immunised pigs.

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The uptake of respiratory syncytial virus (RSV) antigen by cattle dendritic cells was investigated. Pathways of antigen uptake were monitored by flow cytometry using specific tracers and by proliferation assays, which were used to measure the presentation of RSV antigen and ovalbumin. Inhibitors that differentially affected pathways were used to distinguish them. Presentation of RSV antigen, but not ovalbumin, was inhibited by phorbol myristate acetate and filipin, which have been reported to inhibit caveolae, but not by cytochalasin D, amiloride, or mannose. These inhibitors have been reported to block macropinocytosis and other actin-dependent uptake mechanisms, endocytic pathways involving clathrin-coated pits, and the mannose receptor. Furthermore, co-localization of RSV antigen and caveolae was observed by confocal microscopy. Thus, the major route for uptake of RSV antigen by cattle dendritic cells is one mediated by caveolae, adding a pathway of antigen uptake by dendritic cells to those established. J. Leukoc. Biol. 66: 50-58; 1999.

Two antigenic sites recognized by neutralizing monoclonal antibodies (MAbs) directed against the fusion (F) glycoprotein of human respiratory syncytial virus were mapped on the primary structure of the protein by (i) the identification of amino acid substitutions selected in antibody-escape mutants and (ii) the reactivity of synthetic peptides with MAbs. The first site contained several overlapping epitopes which were located within the trypsin-resistant amino-terminal third of the large F1 subunit. Only one of these epitopes was faithfully reproduced by a short synthetic peptide; the others might require specific local conformations to react with MAbs. The second antigenic site was located in a trypsin-sensitive domain of the F1 subunit towards the carboxy-terminal end of the cysteine-rich region. One of these epitopes was reproduced by synthetic peptides. In addition, mutagenized F protein with a substitution of serine for arginine at position 429 did not bind MAbs to the second site. These results are discussed in terms of F protein structure and the mechanisms of virus neutralization.

HighlightsRespiratory syncytial virus (RSV) is a major cause respiratory disease, worldwide.Paediatric and elderly populations are most vulnerable to severe disease.Vaccine development has been hampered by the experience of vaccine-enhanced disease.Animal models do not necessarily predict vaccine efficacy and safety.The strengths and limitations of animal models of RSV infection are summarised.

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Bovine respiratory syncytial virus (BRSV) is an enveloped, nonsegmented, negative-stranded RNA virus and is a major cause of respiratory disease in young calves (44). BRSV is closely related to human RSV (HRSV), which is a major cause of respiratory disease in young children (10), and the epidemiology and pathogenesis of infection with these viruses are similar (44). These features make BRSV infection in calves a good model for the study of HRSV. HRSV and BRSV belong to the Pneumovirus genus within the Paramyxoviridae family. One of the major differences between this genus and all the other Paramyxoviridae is the presence of two nonstructural (NS) genes called NS1 and NS2. These genes code for two proteins, which are abundantly transcribed in virus-infected cells. Comparison of the sequence of the NS proteins of BRSV with that of HRSV subgroup A and B reveals amino acid identities of 69 and 68% for the NS1 protein and 84 and 83% for the NS2 protein, respectively (8, 39).The role(s) of the NS proteins is not fully defined. They are not essential for virus replication in vitro, although the growth of recombinant HRSV and BRSV lacking these proteins is attenuated in cell culture (8,25,42,51). There is evidence that the HRSV NS1 protein coprecipitates with the M protein (19), and in experiments using HRSV minigenomes, the NS1 protein appears to be a strong inhibitor of viral RNA transcription and replication (1). The NS2 protein also appears to be a transcriptional inhibitor but at a lower level than is the NS1 protein (1). The NS2 protein colocalizes with the P and N proteins in infected cells (60) but does not coprecipitate with any viral protein (19). In addition, the NS1 and NS2 proteins of BRSV and HRSV mediate resistance to the antiviral action of alpha/beta inferferons (IFN-␣/␤) (3, 42).Anti-IFN activity has been described for accessory proteins for a number of other negative-stranded RNA viruses. Of those characterized to date, some block the IFN response by hindering the late-stage activation of antiviral genes. For example, the C protein of Sendai virus inhibits STAT1 activation by hampering phosphorylation and by increasing instability (21, 64) and the V protein of simian virus 5 inhibits the activation of IFN-responsive genes by targeting STAT1 for proteasome-mediated degradation (13). Other viral accessory proteins, such as influenza A virus NS1 protein and Bunyamwera virus NSs protein, inhibit the production of IFN-␣/␤ (58, 61).