Animal models of human respiratory syncytial virus disease

Abstract

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...

Controlled human infection with RSV: The opportunities of experimental challenge

“…Extrapolating from pre-clinical models is therefore difficult and they remain imprecise guides to understanding both mechanisms of protection and pathogenesis, as well as the likely clinical efficacy of candidate vaccines and therapeutics [5]. Most animals are at most semi-permissive to human RSV and require large, supra-physiological inocula to become infected.…”

Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

“…Although animal models of RSV infection provide mechanistic insights, they do not recapitulate all aspects of human disease and remain imprecise guides to the clinical efficacy of vaccines (12). Investigation of hospitalized children and high-risk adults allows natural disease to be observed, but cannot correlate prior immune status with susceptibility to infection.…”

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

“…These models provide a more dynamic and flexible setting to test hypotheses in vivo, addressing some of those inquiries regarding the mechanism of disease pathogenesis. Ultimately, animal models are necessary tools to assess the safety and efficacy of novel vaccines and therapeutics during preclinical trials [67].…”

“…Heterologous host-virus models involve the infection of semi-permissive animals like chimpanzees, sheep, cotton rats and mice with human RSV [6,67]. On the other hand, cognate host-virus models are based on other pneumoviruses infecting their natural hosts.…”

“…On the other hand, cognate host-virus models are based on other pneumoviruses infecting their natural hosts. Examples of the latter include bovine RSV (BRSV) and pneumonia virus of mice (PVM) [6,67]. While there are unique advantages and disadvantages to each individual animal model, it is important to realize that not a single experimental system in isolation can be used to answer all the questions regarding the human RSV disease spectrum.…”