The use of a neonatal mouse model to study respiratory syncytial virus infections

Abstract

Respiratory syncytial virus (RSV) infection is the most significant cause of viral death in infants worldwide. The significant morbidity and mortality associated with this disease underscores the urgent need for the development of an RSV vaccine. The development of an RSV vaccine has been hampered by our limited understanding of the human host immune system, which plays a significant role in RSV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which RSV causes disease. Within the past few years, a revolutionary variation on these animal models has emerged -age at time of initial infection -and early studies in neonatal mice (aged <7 days at time of initial infection) indicate the validity of this model to understand RSV infection in infants. This article reviews available information on current murine and emerging neonatal mouse RSV models.

Animal models of human respiratory syncytial virus disease

“…Likewise, specific mouse strains, including New Zealand Black mice (which have inherent impaired macrophage function) (96), and gene-targeted mice deficient for Toll-like receptor (TLR)2, TLR4, TLR6 and TLR7 (65,68,81) show increased susceptibility for hRSV. Unlike in humans, young age in mice is not an important risk factor for severe primary LRTD (51) although age at initial infection as been reported to play a critical role in the development of delayed sequelae of pulmonary dysfunction, with younger mice experiencing increased airway hyperreactivity with enhanced mucus production, eosinophilic inflammation, and Th2 responses upon reinfection during later life (27,29,31).…”

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

“…Our and other laboratories have therefore developed a neonatal mouse model that better mimics RSV disease in infants (4)(5)(6)(7)(8)(9). In this model, neonatal mice (Ͻ7 days old) are infected with RSV and various immunological parameters are measured.…”

“…The neonatal mouse model of RSV infection has proven to be an invaluable model to study and understand RSV pathogenesis in infants (5). Using this model, we have recently demonstrated that interleukin 4 receptor ␣ (IL-4R␣) on Th cells plays a pathogenic role in RSV reinfection-associated immunopathophysiology (4).…”

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

“…Histopathological lesions include perivasculitis and peribronchiolitis, and in some cases, interstitial pneumonia is observed [67,68]. In terms of age, experimentally infected neonatal Balb/c mice develop asthma-like symptoms such as airway hyperreactivity, mucus overproduction, eosinophilia and a distinct Th2-biased response [51, 67,73]. In contrast, RSV infection in adult Balb/c mice induces a Th1-biased response, with high concentrations of IFN-γ in both lung and BALF [68,73].…”

“…In terms of age, experimentally infected neonatal Balb/c mice develop asthma-like symptoms such as airway hyperreactivity, mucus overproduction, eosinophilia and a distinct Th2-biased response [51, 67,73]. In contrast, RSV infection in adult Balb/c mice induces a Th1-biased response, with high concentrations of IFN-γ in both lung and BALF [68,73]. A clear downside of using this animal model is the numerous differences between innate and adaptive immune responses of humans and mice [67].…”