Increased pulmonary secretion of tumor necrosis factor-α in calves experimentally infected with bovine respiratory syncytial virus

Abstract

Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves, of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF-alpha in the BAL fluid of calves killed post inoculation day (PID) 2 and 4 was at the same very low level as in the uninfected control animals. Large amounts of TNF-alpha were detected on PID 6, maximum levels of TNF-alpha were reached on PID 7, and smaller amounts of TNF-alpha were seen on PID 8. The high levels of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period of the infection, as well as BRSV-infected calves free of bacteria reached the same level of TNF-alpha as animals from which bacteria were isolated from the lungs. It is concluded that significant quantities of TNF-alpha are produced in the lungs of the calves on PID 6-7 of BRSV infection. The involvement of TNF-alpha in the pathogenesis of, as well as the anti-viral immune response against, BRSV infection is discussed.

Age-dependent differences in the pathogenesis of bovine respiratory syncytial virus infections related to the development of natural immunocompetence

“…Although still a controversial issue, it has been concluded from a number of studies that immunological factors play a major role in the most severe type of pulmonary damage associated with RSV infection (Coomber et al, 2001;Heegaard et al, 2000;Rontved et al, 2000). This view has evolved from unusual epidemiological patterns of RSV disease and from attempts to interpret the altered reactivity to RSV infections observed after primary vaccination.…”

Bovine respiratory syncytial virus infection

“…This protein is 81 AA [111] and varies by up to 13% between different BRSV isolates [109]. The SH protein of HRSV exists as different forms, SHg (13-15 kDa), SHp (21-30 kDa), non-glycosylated SH0 (7.5 kDa) and a nonglycosylated form SHt (4.8 kDa) which is derived from initiation at a second methionine in the open reading frame (ORF) [4,111].…”

“…Maternally derived antibodies provide at least partial protection against clinical signs after natural and experimental BRSV infection [11, [68][69][70]. Although virus shedding has occasionally been detected upon experimental BRSV re-infection, little or no clinical disease is observed in reinfected animals [69,109,134,145]. Similar to observations made for HRSV [67], exacerbated clinical signs have been observed following a natural BRSV infection in animals immunised with inactivated vaccines [5, 47,119].…”

Animal Pneumoviruses: Molecular Genetics and Pathogenesis

“…In the study performed by Philippou et al (287), lungs from animals sacrificed at 12 weeks postinoculation were atelectatic with evidence of bronchiolar obstruction and profound inflammatory infiltration. Disease progression has been associated with increased expression of IL-2, IL-4, and/or gamma interferon in cells drained from pulmonary lymph (139,214) and in peripheral blood mononuclear cells (257), detection of tumor necrosis factor alpha and leukotriene B4 in respiratory secretions (302,308), and elevations in levels of serum acute-phase response proteins (171). Aside from the challenging aspects of working with large experimental animals, research in this field is hampered by the fact that there are comparatively few bovine cytokine gene sequences available in the public domain and even fewer commercially available reagents.…”