Pulmonary lesions induced by 3-methylindole and bovine respiratory syncytial virus in calves

Our objectives were to describe the ultrastructural morphogenesis of pulmonary lesions induced by 3-methylindole in 30- to 45-day-old Holstein calves and to determine whether toxic exposure to 3-methylindole exacerbates pulmonary lesions induced by bovine respiratory syncytial virus. Administration of 3-methylindole (0.25 g/kg) to calves resulted in interstitial edema and ultrastructural swelling of type-I alveolar epithelial cells and nonciliated bronchiolar epithelial cells as early as 4 to 6 hours after intraruminal administration. More severe alveolar edema containing protein was associated with swelling of capillary endothelial cells at 2 days after administration. Proliferation of type-II alveolar epithelial cells was first observed at 2 days after 3-methylindole administration, and marked hyperplasia of type-II epithelial cells and nonciliated bronchiolar epithelial cells was evident by 4 days after administration. Pulmonary cytochrome P-450 monooxygenase concentrations decreased significantly (P less than 0.001) by 12 hours after administration and did not increase significantly again by 8 days after administration. Calves were inoculated with bovine respiratory syncytial virus 3 days after administration of 3-methylindole, and pulmonary lesions were assessed 5 days after viral inoculation. Viral replication was demonstrated by fluorescence microscopy for viral antigen or by transmission electron microscopy in ciliated and nonciliated airway epithelial cells. Viral antigen was identified infrequently in alveolar macrophages and in type-II alveolar epithelial cells. 3-Methylindole exposure in calves did not result in more widespread distribution of viral antigen in alveolar tissue of respiratory syncytial virus-inoculated calves or in significant enhancement of viral pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental bovine respiratory syncytial virus infection in conventional calves: ultrastructural respiratory lesions

The morphogenesis and repair of airway and alveolar injury induced by bovine respiratory syncytial virus (BRSV) was studied ultrastructurally in conventional calves to characterize pulmonary cell types susceptible to viral infection and cytopathologic changes associated with infection. Viral nucleocapsids and budding virions were present in tracheal and bronchial ciliated and nonciliated epithelial cells and mucous cells 3, 5, and 7 days after inoculation and in bronchiolar ciliated and nonciliated epithelial cells 5 days after inoculation. Mild interstitial pneumonia was observed 5 days after inoculation and was characterized by swelling of type 1 and type 2 alveolar epithelial cells, interstitial edema, and infiltration by lymphocytes and macrophages. Viral assembly and release in tracheal and bronchial epithelial cells was associated with loss of cilia from ciliated cells, formation of syncytial epithelial cells, swelling of mitochondria and endoplasmic reticulum, and cell necrosis. Neutrophils, lymphocytes, and macrophages were present in close association with the viral-infected and damaged epithelial cells. There was intercurrent hyperplasia of basal epithelial cells that, in association with other epithelial lesions, resulted in the loss of normal ciliated epithelium in these airways 5 and 7 days after inoculation. Regeneration of airway epithelium was largely completed by 10 days after inoculation, except in 1 of 4 calves that had failure of epithelial repair and that developed secondary bacterial pneumonia. Pulmonary ultrastructure in BRSV-inoculated calves 30 days after inoculation was indistinguishable from that in controls. The results demonstrated that BRSV can induce reversible alterations in airway epithelium, which may cause depression of mucociliary clearance and thereby enhance susceptibility to bacterial infection.     

Ultrastructural features of alveolar lesions in induced respiratory syncytial virus pneumonia of calves

Ultrastructural changes occurred in alveolar epithelium in the acute and repair stages of induced respiratory syncytial virus pneumonia induced in eight calves (calf Nos. 1-7, 3 to 6 days old and calf No. 8, 2 weeks old), using a bovine strain of respiratory syncytial virus. Five of the calves were Friesians, three were Hereford x Friesians, and all were male. Tissues from three mock-infected control calves (two Friesian, one Hereford x Friesian) were also examined. Evidence of respiratory syncytial virus infection was observed in both type I and type II pneumocytes from day 4 to day 8 after infection. Infection of type I pneumocytes frequently resulted in necrosis. The response of type II pneumocytes to respiratory syncytial virus infection varied and included hypertrophy, hyperplasia, and syncytial formation. In some infected type II pneumocytes, there were numerous irregular projections of the cell surface, associated with viral budding. Hypertrophy and hyperplasia of type II pneumocytes, epithelial syncytium formation, and irregular cytoplasmic projections from epithelial cells caused considerable thickening of respiratory membrane and occlusion of alveolar lumina. Neutrophils were frequently observed in close association with virus-infected epithelial cells, but evidence of respiratory syncytial virus infection and replication was not observed in alveolar macrophages or neutrophils. Proliferation of type II pneumocytes appeared to play a major role in maintaining the integrity of the alveolar epithelium during the acute stage of the experimental pneumonia. Increased numbers of type II pneumocytes were present on alveolar walls, particularly from 4 to 8 days after infection, and some alveoli were lined entirely by this cell type. In some areas, however, squamous epithelial cells were also involved in covering exposed alveolar basement membrane.     

Interaction of bovine respiratory syncytial virus with bovine alveolar macrophages in vivo: effects of virus infection upon selected cell functions.

The effect of bovine respiratory syncytial virus (BRSV) upon alveolar macrophage (AM) function was investigated using an in vivo calf inoculation model. Alveolar macrophages were collected sequentially from live calves at multiple time points during the 14 day period following viral inoculation. Alveolar macrophages from bronchoalveolar lavage fluids were purified by density gradient centrifugation (> 95% AM) prior to in vitro evaluation of cell functions. There were significant but variable and inconsistent differences in the functions of AM from the BRSV inoculated calves compared to the control calves. Fc-receptor mediated phagocytosis was either increased or unchanged by BRSV inoculation. Nonopsonized phagocytosis was decreased during the early postinoculation period and later increased. There was a variable effect on AM phagosome lysosome fusion with increased fusion activity on postinoculation days 2 through 5, 7 and 12 but reduced activity on days 6 and 10. The AM respiratory burst, as measured by nitroblue tetrazolium dye reduction, was essentially unaffected with a reduction in activity on day 10 only. In this model, BRSV inoculation of calves primarily resulted in an alteration of the membrane associated phagocytic functions of the alveolar macrophages (p < 0.05).     

Studies on the pathogenesis and interspecies transmission of respiratory syncytial virus isolated from sheep

Inoculation of lambs with an ovine isolate of respiratory syncytial virus (RSV) by a combined intranasal and intratracheal route resulted in mild respiratory tract illness, with respiratory tract lesions. Lung lesions were characterized by bronchitis and bronchiolitis, hyperplasia of bronchial and bronchiolar epithelium, peribronchiolar and perivascular accumulations of lymphocytes, alveolar septal thickening, and collapse. Respiratory syncytial virus was recovered from the respiratory tract of inoculated lambs, and RSV antigen was demonstrated by immunoperoxidase staining of bronchiolar and alveolar epithelial cell in pneumonic lesions of lambs euthanatized on post-inoculation days 5 and 6. Other primary respiratory tract pathogens were not isolated. Clinical signs of respiratory tract illness or respiratory tract lesions did not develop in the in-contact control lamb. Inoculation of the ovine RSV isolate into calves and deer fawns resulted in infection in both species, and at necropsy, pneumonic lesions were present. A mild to moderate respiratory tract illness developed in the calves, but clinical disease was not seen in the fawns. Lung lesions in fawns were similar to those seen in lambs; lesions in calves were characterized by collapse, scattered areas of parenchymal necrosis, and bronchiolitis. Respiratory syncytial virus was reisolated from the lower respiratory tract of inoculated calves and fawns, and immunoperoxidase-positive epithelial cells were seen in pneumonic lesions. Other primary respiratory pathogens were not detected. Respiratory syncytial virus infection was not demonstrable in control animals that were in contact with inoculated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructural features of lesions in bronchiolar epithelium in induced respiratory syncytial virus pneumonia of calves

Ultrastructural changes were observed in bronchioles in acute and repair stages of respiratory syncytial virus pneumonia induced in eight young calves (calf Nos. 1-8) using a bovine strain of respiratory syncytial virus. Five of the calves were Friesians and three were Hereford x Friesians and all were male. Tissues from three mock-infected control calves (two Friesian, one Hereford x Friesian) were also examined. Calves were from 3 to 6 days old at the time of first inoculation, with the exception of calf No. 8, which was 2 weeks old. In the acute stage of the induced pneumonia, evidence of respiratory syncytial virus replication and release was demonstrable in both ciliated and non-ciliated bronchiolar epithelial cells, with the virus-releasing process most obvious at 4 and 5 days after infection. Respiratory syncytial virus infection of bronchiolar epithelium was associated with various changes, including hypertrophy, hyperplasia, and formation of syncytia. Necrosis of epithelial cell structures usually appeared to be preceded by their desquamation from bronchiolar walls. Respiratory syncytial virus infection resulted in considerable damage to the bronchiolar ciliary apparatus. Such damage was seen as early as 1 day post-infection and was still obvious at 10 days post-infection. Neutrophils were closely associated with respiratory syncytial virus infected epithelial cells and evidence of neutrophil fusion with infected epithelial cells was seen. These observations suggest that neutrophils may be involved in killing respiratory syncytial virus infected cells and that neutrophils might play an important role in early antiviral defense against respiratory syncytial virus at a time when antibody levels are low and other cellular defenses are not fully in play. Bronchiolar repair was evident from 6 days after infection and was well advanced at 10 and 13 days after infection.     

Interaction of bovine respiratory syncytial virus and Pasteurella haemolytica in the ovine lung

The potential synergistic effect of bovine respiratory syncytial virus (RSV) and Pasteurella haemolytica in the production of pneumonia after aerosol/intranasal infection of conventionally reared lambs was evaluated. A mild clinical response was observed in lambs given virus and/or bacteria. Gross pulmonary lesions were seen in 3 of 6 lambs given RSV and then P haemolytica 3 or 6 days later, respectively (groups D and E), and in 1 lamb of 5 given virus and bacteria simultaneously (group G). Gross lesions were not seen in control sheep (group A), in lambs given virus or bacteria alone (groups B and C), or in lambs exposed to bacteria and then virus 3 days later (group F). Bovine RSV and P haemolytica were recovered from the lungs of 5 of 7 lambs with macroscopic lesions. Gross pulmonary lesions were cranioventral firm areas of red consolidation. Microscopically, the predominant lesion was a suppurative bronchopneumonia. Bovine RSV was recovered from the nasal cavity of 8 of 27 (30%) lambs given RSV during days 3 to 6 after viral inoculation, including 1 lamb in group B, 2 in groups D, E, and F, and 1 in group G. Pasteurella haemolytica was recovered from the nasal cavity of 9 of 28 (32%) inoculated lambs, including 2 lambs from groups C and E, 3 in group D, and 1 in groups F and G. Viral antigen, as determined by immunofluorescence, was concentrated mainly in individual cells in alveolar walls, some alveolar macrophages, and a few bronchiolar epithelial cells. In vitro alveolar macrophage assays indicated decreased numbers of Fc receptors on those macrophages collected from lambs given RSV 6 days before P haemolytica infection, as compared with that in the other groups. These cellular defects disappeared after 24 hours of culture. Seemingly, bovine RSV does facilitate P haemolytica pulmonary infection in conventional, immuno-competent lambs and provides evidence for decreased Fc receptors on alveolar macrophages.     

Replication of parainfluenza type-3 virus and bovine respiratory syncytial virus in isolated bovine type-II alveolar epithelial cells.

The objectives of our research were to determine whether bovine pulmonary type-II alveolar epithelial cells could be isolated from bovine lung and maintained in tissue culture and to determine whether isolated bovine type-II alveolar epithelial cells would support productive viral replication of bovine parainfluenza type-3 virus and bovine respiratory syncytial virus. Type-II alveolar epithelial cells were isolated from lungs of 4- to 7-day-old male Holstein calves by enzymatic dissociation of pulmonary tissue with trypsin and by separation of cells with the use of filtration and centrifugation on continuous Percoll gradients. Cells were further separated by panning on IgG-coated plastic plates and by lectin binding. Isolated type-II alveolar cells were maintained on basement membrane-coated tissue cultured plates. In culture, type-II cells formed alveolar structures and maintained other cytologic features of type-II cells, including osmiophilic lamellar inclusions. Cell cultures were inoculated with and supported productive replication of bovine parainfluenza type-3 virus and bovine respiratory syncytial virus. This was determined by recovery of infectious viruses from inoculated cell cultures and by identification of viral structures in type-II alveolar epithelial cells by transmission electron microscopy.     

Clinical and pathological observations on spontaneous bovine respiratory syncytial virus infections in calves

A clinical, pathological and microbiological study was made of acute spontaneous bovine respiratory syncytial virus infection in calves. Characteristic features were atelectatic areas, which had an exudative and, or, necrotising bronchiolitis with syncytial giant cells in the epithelial lining and in the lumina of these bronchioles. Restricted to these areas both bronchiolar and alveolar immunofluorescence for bovine respiratory syncytial virus were seen. Complications were severe interstitial oedema, interstitial emphysema and a catarrhal or fibrinous pneumonia due to secondary bacterial invasion.     

Effects of 4-ipomeanol on bovine parainfluenza type 3 virus-induced pneumonia in calves.

Previous research has demonstrated that 4-ipomeanol toxicosis can enhance the severity of para-influenza virus-induced pneumonia in mice. The objectives of this study were to determine whether calves are susceptible to 4-ipomeanol-induced enhancement of parainfluenza type 3 viral pneumonia and to determine whether 4-ipomeanol alters pulmonary replication of parainfluenza virus. Male Holstein calves were injected with either 4-ipomeanol (3 mg/kg) or vehicle (polyethylene glycol) 3 days prior to intratracheal inoculation with either parainfluenza virus or sham inoculum of culture medium. Calves in the four treatment groups (ipomeanol-parainfluenza, ipomeanol-medium, vehicle-parainfluenza, and vehicle-medium) were necropsied at 5 days after inoculation with parainfluenza virus or medium. The lungs were studied by correlated methods of light and electron microscopy, digitizing morphometry and pulmonary lavage to quantitate the severity of pneumonia. Pulmonary viral titers were determined, and viral antigen was identified in the lung by immunoperoxidase technique. The calves in the ipomeanol-virus treatment group had over a 9-fold higher (P less than 0.05) volume density of virus-induced interstitial pneumonia than did the calves in the other three treatment groups. This 4-ipomeanol-enhanced viral pneumonia was associated with significantly greater (P less than 0.05) numbers of pulmonary macrophages and neutrophils in the lavage fluid and higher (P less than 0.05) pulmonary titers of pulmonary infectious parainfluenza virus. Four-ipomeanol-enhanced viral pneumonia was characterized in part by extensive hyperplasia of type II alveolar epithelial cells and by dense aggregates of macrophages and neutrophils in alveolar spaces and interalveolar septa. The results indicate that 4-ipomeanol exacerbates interstitial pneumonia in calves induced by bovine parainfluenza type 3 virus.     

Effect of respiratory infections caused by bovine herpesvirus-1 or parainfluenza-3 virus on bovine alveolar macrophage functions

Calves, 90 to 130 days old, were inoculated with bovine herpesvirus-1 (BHV-1) or parainfluenza-3 (PI-3) virus. Pulmonary lavage specimens obtained from calves before virus inoculation contained 98% alveolar macrophages (AM) and 1% neutrophils. Six days after inoculation, the mean percentage of neutrophils in lavage specimens had significantly increased to 7.9 +/- 6.0% in BHV-1-inoculated calves and to 18.3 +/- 9.9% in PI-3 virus-inoculated calves, reflecting viral-induced pulmonary inflammation that was confirmed histologically. Approximately 75% of AM obtained before virus inoculation had Fc surface receptors, and 60% had C3b receptors. Six days after inoculation, the percentage of AM with Fc and C3b receptors was significantly reduced to 69.7 +/- 8.6% and 27.1 +/- 19.8%, respectively, in BHV-1-inoculated calves and to 67.8 +/- 15.4% and 38.8 +/- 23.2%, respectively, in PI-3 virus-inoculated calves. Alveolar macrophages obtained after virus inoculation were significantly impaired in their ability to phagocytize opsonized Staphylococcus epidermidis, but were able to kill ingested bacteria. Alveolar macrophage dysfunctions caused by BHV-1 or PI-3 respiratory infection did not differ appreciably.     

Effect of "in vitro" exposure of bovine alveolar macrophages to different strains of bovine respiratory syncytial virus.

A vaccine strain of respiratory syncytial (RS) virus and an isolate from pneumonic calves (AC2) were inoculated onto cultures of bovine alveolar macrophages recovered by lung lavage, and the functional properties of the cells observed over a period of 10 days. In most cultures no infectious virus was produced although immunofluorescence indicated the presence of virus antigens in some cells. No significant difference was noted between infected and control macrophage cultures in their capacity to phagocytose latex particles (neutral phagocytosis), although the ability to phagocytose complement-coated Candida krusei cells was affected, particularly with the AC2 strain after 6 days. Killing of C. krusei cells was slightly affected by infection of macrophages with the vaccine strain and was dramatically affected by infection with strain AC2. C3b and Fc receptor expression was adversely affected by both virus strains. Production of neutrophil chemotactic factors was increased in cultures infected with both strains, but was greater with AC2, suggesting that some properties of the cells were activated.     

Effects of two adenoviruses (type 1 and type 8) on functional properties of bovine alveolar macrophages in vitro.

Cultures of bovine alveolar macrophages were inoculated with type-1 and type-8 adenoviruses, initially isolated from calves with respiratory tract disease, and functional properties of the cells were observed over a period of 10 to 11 days. Both viruses replicated in macrophages; viral titers were low (less than 3.75 log10 TCID50/0.1 ml), and intranuclear inclusions were detected by indirect immunofluorescence in 5 to 10% of the cells from 3 days after inoculation. Highest titers were induced by type-1 adenovirus, which also induced the greatest functional changes. Expression of Fc and complement receptors was reduced by both viruses, although the greatest effects were seen with type 1. Phagocytosis of Candida krusei cells was reduced following type 1 infection, whereas phagocytosis in type-8-infected cells was not different from that of noninfected macrophages. Ability to kill ingested Candida cells also was reduced following type-1 infection, whereas type-8-infected macrophages had lower killing ability only at 2 to 4 days after inoculation. Neither virus had substantial effects on the production of neutrophil chemotactic factors by the macrophages.     

An immunoperoxidase method of detecting respiratory syncytial virus antigens in paraffin sections of pneumonic bovine lung

Using an avidin-biotin-peroxidase complex immunoperoxidase staining method, respiratory syncytial virus (RSV) antigen was demonstrated in glutaraldehyde-fixed, paraffin-processed lung sections from calves with induced RSV pneumonia. The virus also was detected in formalin-fixed, paraffin-processed lung sections from calves with naturally occurring RSV pneumonia. Specific immunoperoxidase staining was detected within the cytoplasm of epithelial cells and syncytia in small bronchi, bronchioli, and alveoli. Staining also was detected within exudates in airway lumina and in mononuclear and multinucleate cells within alveolar lumina. Optimal intensity of staining was achieved by proteolytic enzyme treatment of lung sections, using 0.1% pronase and overnight incubation in diluted primary antiserum. The distribution of antigen had a close correlation with presence of lesions. Antigen-staining patterns were similar in lung tissue from calves with naturally occurring and induced RSV disease.     

Pathological, ultrastructural, and immunohistochemical changes caused by Lelystad virus in experimentally induced infections of mystery swine disease (synonym: porcine epidemic abortion and respiratory syndrome (PEARS))

The pathogenicity and pathogenesis of Lelystad virus was studied in six 6-day-old SPF piglets. A third passage of the agent was propagated on porcine alveolar macrophages and intranasally inoculated into pigs. Pigs were killed at hours 24, 48, 60, and 72, and on days 6 and 8 after inoculation. From day 2 on pigs developed diffuse interstitial pneumonia with focal areas of catarrhal pneumonia, and from this day on splenic red pulp macrophages were enlarged and vacuolated. Lelystad virus was re-isolated from the lungs of infected pigs from day 2 after inoculation. Lelystad virus antigens were detected by immunohistochemical techniques in bronchiolar epithelium and alveolar cells, and in spleen cells of infected pigs from day 2 after inoculation. Ultrastructural examination of tissues by electron microscopy revealed degenerating alveolar macrophages and epithelial cells in lungs and nasal mucosa, with excessive vacuolation of the endoplasmic reticulum. Although the respiratory tract seems to be the target organ for this virus, macrophages in other organs, such as the spleen, can also be infected. This preference for macrophages may impair immunological defences.     

Effect of vaccination on cell populations in lung washes from calves after infection with respiratory syncytial virus

The inflammatory response in the air-passages of the lungs of calves after intranasal inoculation with respiratory syncytial virus (RSV) was compared in RSV-vaccinated and control animals. Total cells recovered from lung washings remained the same; however, the fold by eight days after infection and the type of cells changed from a predominance (85 per cent) of macrophages to equal proportions of macrophages and neutrophils (45 per cent) during the course of infection. The absolute numbers of neutrophils rose by 15-fold. In contrast, when RSV-vaccinated calves were challenged, the total number of cells recovered from lung washings remained the same; however, the numbers of macrophages decreased and the numbers of neutrophils increased by fivefold. Cytological studies of the lung washings revealed no evidence of an exacerbated inflammatory response in RSV-vaccinated calves. Levels of virus replication were significantly reduced in RSV-vaccinated compared with control animals.     

Flow cytometric analysis of bronchoalveolar lavage fluid immune dynamics in calves

Understanding the immune dynamics in the respiratory mucosa of calves is necessary for a good management of bovine respiratory disease. Immune dynamics in the respiratory mucosa in humans and experimental animals has been assessed by flow cytometric analysis of bronchoalveolar lavage fluid (BALF); however, few reports have addressed this subject in calves. The aim of this study was to establish a universal method to analyze bronchoalveolar lavage fluid (BALF) by flow cytometry and to obtain basic knowledge of bovine respiratory mucosal immune dynamics. We investigated the immune cell populations in BALF and evaluated the surface antigen expression of alveolar macrophages in calves using flow cytometer. To further analyze the surface antigen variation observed in alveolar macrophages in detail, stimulation assays were performed in vitro. BALF cells were separated into three distinct populations based on their light scatter plot, which were considered to be macrophages, lymphocytes, and neutrophils. In most individuals, most of the BALF immune cells were alveolar macrophages, but an increased proportion of lymphocytes and neutrophils was observed in some individuals. Analysis of each surface antigen expression in alveolar macrophages showed that CD21 and MHC class II expression changed in response to changes in the leukocyte population. Moreover, when alveolar macrophages were stimulated with interferon-γ in vitro, the expression of CD21 was drastically reduced and MHC class II was increased, suggesting that functional changes in alveolar macrophages themselves are involved in the immune dynamics.     

Characterization and identification of a bovine respiratory syncytial virus isolated from young calves.

Two identical viruses designated 371 and 375 were recovered from nasal secretions of 2 of 7 calves in a beef cow-calf herd in which calves (45 to 105 days of age) had signs of acute respiratory tract disease. The cytopathic, morphologic and physico-chemical characteristics of the isolates were those of bovine respiratory syncytial virus. Although a humoral antibody response to bovine respiratory syncytial virus was not observed, it was concluded that this virus probably had a part in the respiratory tract disease in these calves.     

Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus

An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia.     

Prevention of bovine respiratory syncytial virus infection and clinical disease by vaccination

A double blind field trial was carried out with a live attenuated bovine respiratory syncytial virus vaccine. The trial involved 530 calves, two to 10 months old, on 27 dairy farms, where respiratory problems due to bovine respiratory syncytial virus infections had been observed during the preceding year. In 17 herds either all calves were vaccinated (nine groups) or all calves received a placebo (eight groups). In 10 herds half the number of calves were vaccinated and the other half kept as non-vaccinated controls. Calves were vaccinated intramuscularly twice with an interval of four to five weeks. These groups were under regular clinical observation and animals were tested periodically for antibodies to bovine respiratory syncytial virus and parainfluenza type 3 virus. Serological examination indicated that no bovine respiratory syncytial virus infection had occurred prior to the first vaccination in August. Vaccination did not cause adverse reactions. Low concentrations of neutralising and complement fixing antibodies were induced by vaccination and a sharp increase of antibody titres was observed after natural infection of vaccinated animals. Infections with bovine respiratory syncytial virus occurred in six out of eight non-vaccinated groups, in nine out of 10 partly vaccinated groups and in only two out of nine completely vaccinated groups. Virus infection in completely vaccinated groups was significantly reduced compared with partly vaccinated and non-vaccinated groups. The incidence of bovine respiratory syncytial virus lower respiratory disease was significantly reduced in completely vaccinated groups compared to non-vaccinated groups. Generally only mild signs of upper respiratory disease were present in completely vaccinated groups after bovine respiratory syncytial virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)