Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM

A functional <it>tonB</it> gene is required for both virulence and competitive fitness in a chinchilla model of <it>Haemophilus influenzae</it> otitis media

<p><b>Abstract</b></p> <p><b>Background</b></p> <p><it>Haemophilus influenzae</it> requires heme for aerobic growth and possesses multiple mechanisms to obtain this essential nutrient.</p> <p><b>Methods</b></p> <p>An insertional mutation in <it>tonB</it> was constructed and the impact of the mutation on virulence and fitness in a chinchilla model of otitis media was determined. The <it>tonB</it> insertion mutant strain was significantly impacted in both virulence and fitness as compared to the wildtype strain in this model.</p> <p><b>Conclusions</b></p> <p>The <it>tonB</it> gene of <it>H. influenzae</it> is required for the establishment and maintenance of middle ear infection in this chinchilla model of bacterial disease.</p

Immunopathogenesis of polymicrobial otitis media

OM, or inflammation of the middle ear, is a highly prevalent infection in children worldwide. OM is a multifactorial disease with multiple risk factors, including preceding or concurrent viral URT infection. Hence, OM is also a polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM are replete; however, all are predicated on the general principle of compromise of primary host airway defenses. Thus, despite an as-yet incomplete understanding of the molecular mechanisms involved in bacterial superinfection of a virus-compromised respiratory tract, the URT viruses are known to induce histopathology of airway mucosal epithelium, up-regulate expression of eukaryotic receptors used for bacterial adherence, alter the biochemical and rheological properties of airway mucus, and affect innate and acquired host immune functions, among others. Although discussed here in the context of OM, during preceding or concurrent viral infection of the human respiratory tract, viral impairment of airway defenses and the resulting predisposition to subsequent bacterial coinfection are also known to be operational in the mid and lower airway as well