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

Antonis, A.F.G.; Jong, Marina C. de; Poel, Wim van der; Most, Robbert G. van der; Stockhofe-Zurwieden, Norbert; Kimman, Tjeerd G.; Schrijver, R.S.

doi:10.1099/vir.0.020842-0

Cited by 38 publications

(43 citation statements)

References 36 publications

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“…Most importantly, there is a similar age dependency in the development of bRSV disease: more severe LRTD occurs in young calves, whereas neonatal infection follows a nonspecific pattern of disease (4,52,111). bRSV infection in calves causes overt clinical signs of URTD and LRTD (peak at day 7 after experimental inoculation), such as nasal discharge, cough, tachypnea with chest retractions, wheezing, hypercapnia, and hypoxemia (4,6,25,49,52,111,115). General symptoms, including fever, anorexia, and reduced activity, are also observed.…”

Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

“…Finally, there is evidence of extensive apoptosis of lung epithelial cells (115). In addition, calves with bRSV LRTD show a strong lung neutrophil and macrophage response, whereas effector lymphocytes are detected in lower numbers in lung tissue or BALF (4,69,115). bRSV LRTD is associated with an increase in the levels of IFN-␥, TNF-␣, and IL-6 in BALF (4).…”

Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

“…The disease symptoms in bRSV disease in calves is associated with prominent histopathological changes in lung tissue, involving bronchiolitis and interstitial pneumonia with patchy areas of consolidation, atelectasis or air trapping, and in some cases the deposition of hyaline membranes (4,21,49,66,69,115). Occasionally emphysematous bullae are found in animals with severe bRSV disease (49,115).…”

Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

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Animal models of human respiratory syncytial virus disease

Reinout

Domachowske

Rosenberg

2011

American Journal of Physiology-Lung Cellular and Molecular Phys

173

228

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Bem RA, Domachowske JB, Rosenberg HF. Animal models of human respiratory syncytial virus disease. Am J Physiol Lung Cell Mol Physiol 301: L148 -L156, 2011. First published May 13, 2011; doi:10.1152/ajplung.00065.2011.-Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research. respiratory virus; pneumovirus; rodent; inflammation Human RSV Disease: Why Model?Human respiratory syncytial virus (hRSV) is among the most important respiratory pathogens in young children worldwide. hRSV infection and transmission result in community outbreaks with peak activity during the winter months in areas with temperate climates, whereas hRSV disease activity is observed on a more continuous basis throughout the year in tropical regions (119). In a recent evaluation of the global burden of hRSV-associated acute lower respiratory tract disease (LRTD), Nair and colleagues (82) noted that, each year, over 33 million children under the age of 5 yr are affected by this disease, leading to over 3 million hospitalizations and almost 200,000 deaths. The annual costs of health care associated with hRSV infection among children in the US alone are over $600 million (86). In addition, a growing body of evidence suggests that hRSV infection results in substantial morbidity among the elderly and in adults with underlying chronic illnesses, further highlighting both the healthcare-related and economic burden of hRSV disease (44).At this writing, there is no licensed vaccine for hRSV, and there are no specific treatment options for severe disease. There is presently no clear evidence supporting the routine use of the antiviral ribavirin (114), inhaled or systemic corticosteroids (12, 87), or bronchodilators (47) as mainstays of acute therapy in nonimmunosuppressed infants and children. The humanized monoclonal anti-RSV F protein, palivizumab, is approved for prophylactic use in high-risk infants only (41, 72), and thus this modality does not presently address the burden of disease among those with no apparent risk factors (55).Modeling human hRSV disease in vivo is an indispensable step in the search for novel therapies and preventive measures for hRSV disease. Animal models provide for t...

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Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

Section: Cognate Host-pneumovirus Modelsmentioning

confidence: 99%

See 1 more Smart Citation

Animal models of human respiratory syncytial virus disease

Reinout

Domachowske

Rosenberg

2011

American Journal of Physiology-Lung Cellular and Molecular Phys

173

228

View full text Add to dashboard Cite

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“…Although RSV infection in chimpanzees causes profuse rhinorrhea, it has not resulted in LRTI (3). RSV infection in owl monkeys (27), cebus monkeys (9) (30), bonnet monkeys (26), cynomolgus macaques (8), and African Green monkeys (17) results in histological evidence of mild interstitial pneumonia, but these animals have not developed tachypnea or hypoxia.…”

mentioning

confidence: 99%

Infant baboons infected with respiratory syncytial virus develop clinical and pathological changes that parallel those of human infants

Papin

Wolf

Kosanke

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in Ͼ300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons (Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for Ն14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a muchneeded model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines. interstitial pneumonia; bronchiolitis; baboon model; animal models; respiratory syncytial virus vaccine RESPIRATORY SYNCYTIAL VIRUS (RSV) is the most important respiratory pathogen of early life. RSV infection, in the form of interstitial pneumonia and bronchiolitis, annually results in Ͼ120,000 hospitalizations in the United States of America and Ͼ300,000 deaths worldwide (21, 24). RSV lower respiratory tract infection (LRTI) in infancy also may predispose to the development of childhood asthma (33). Despite the considerable impact of RSV infection, there is no approved vaccine and no effective specific form of therapy. The lack of an appropriate animal model has resulted in an incomplete understanding of the pathophysiology of the disease and an inability to evaluate the safety and efficacy of vaccines and pharmacological agents. An animal model developing clinical and pathological manifestations similar to those of human infants with RSV infection would provide a significant step toward overcoming these problems. To reflect human disease, an appropriate animal model should develop tachypnea, reduced oxygenation, and interstitial and peribronchiolar inflammation with obstruction of the bronchiolar lumen by invading leukocytes and exfoliated epithelial cells following infection. These manifestations should be most prominent in an infant...

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“…Nevertheless BRSV re-infection can occur through life, although becoming less severe with increase in age. The capacity to produce pro-inflammatory tumor necrosis factor alpha appeared to increase with age, and may explain the age-dependent differences in respiratory syncytial virus pathogenesis (Antonis et al, 2010). Valarcher and Taylor (2007) mentioned age as important risk factors associated with BRSV.…”

Section: Resultsmentioning

confidence: 99%