Pathogenesis of respiratory syncytial virus infection in the murine model

Abstract

There is a wide spectrum of illness caused by respiratory syncytial virus (RSV) infection that is caused in large part by host-related factors, such as age of the patient and degree of host immunocompetency. Although the vast majority of persons infected with RSV experience symptoms of mild upper respiratory tract infection, in some people these infections cause significant morbidity and are sometimes fatal. Although a great deal of investigation in both humans and animals has explained the timing and tropism of RSV infection and the general principles by which the immune system responds to this infection, at present we only partially understand the disparity in illness severity that can occur. This article briefly reviews the clinical sequelae of RSV infection and then focuses on the mechanisms of viral pathogenesis.

Figure 1.

Murine model of respiratory syncytial virus infection. Anesthetized mice can be inoculated intranasally with high-titer respiratory syncytial virus (RSV) stocks to establish infection in the upper and lower respiratory tract. Virus titer peaks in nasal and lung tissue between Days 3 and 6 after inoculation. Illness begins on Day 5, peaks between Days 8 and 10, and resolves by Day 12. Illness is temporally associated with the level of mononuclear cell infiltration into lung. A number of clinical, physiologic, cellular, and molecular endpoints can be measured in the system, providing the opportunity to define mechanisms and correlates of disease. These assays are particularly informative when designed to measure in vivo processes at a moment in time, and avoid in vitro manipulations. BAL = bronchioalveolar lavage; CTL = cytotoxic T lymphocyte; FACS = fluorescence-activated cell sorting; PFU = plaque-forming unit; RPA = RNAse protection assay.