Immune-mediated disease pathogenesis in respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in persons at both extremes of age. Wheezing is a cardinal sign of infection and the illness is associated with an increased incidence of childhood asthma. Data from both humans and animal models have linked severe disease in infants and the syndrome of vaccine-enhanced illness with an aberrant composition of CD4 + T cells, suggestive of an exaggerated Th2 response. Studies in murine models have shown that prior vaccination, coexisting allergic inflammation, or direct modulation of the cytokine milieu can profoundly influence the immune response to RSV and thereby affect the expression of disease. in addition, there are intrinsic antigenic properties of the RSV G glycoprotein that promote Th2 responses and eosinophilia. This paper proposes an integrated working model of how host and virus factors interact to determine the characteristics of RSV-induced illness. This model suggests strategies for the development of new vaccine and immunotherapeutic interventions, and creates a framework for asking additional questions about the immunopathogenesis of RSV. (C) 2000 Elsevier Science B.V, All rights reserved.