chapter  12
20 Pages

Animal Models of Viral Respiratory Infections

The gas exchange function of the lung and vast mucosal surface area together make this site a prime portal of entry for infection. Among the pathogens that may enter and cause respiratory infections are viruses such as influenza, parainfluenza, respiratory syncytial virus (RSV), rhinoviruses, and adenoviruses. Much of the research on the host-pathogen interaction during these infections has necessarily been done in animal models, particularly mouse. The central issues have been the elucidation of those immune mechanisms that may be particularly involved in rapid viral clearance, on the one hand, or with exacerbated lung pathology on the other. These concerns bear directly on the design of rational vaccines that will be effective but safe. In this chapter we review some of the evidence generated from animal models that select out the protective from the pathogenic mechanisms in respiratory virus infections, and discuss the related issue of whether viral infections or the responses to them are involved in the development of asthma. Understanding of the molecular pathogenesis of asthma is still in its infancy. For example, it is now clear that multiple genes are involved, but the identity of only a few of these candidates is known. One clear starting point is that susceptibility is associated with the balance of Th1 and Th2 cytokines in the lung. As discussed below, a major driving force for the

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cytokine milieu in the lung comes from viral infection. Furthermore, many of the lessons learnt from studying T-lymphocyte-cytokine responses during viral infection are pertinent to the analysis of asthma and the design of immumodulatory therapies.