Rat coronavirus infection of alveolar type I cells causes neutrophil recruitment followed by resolution of infection (45.28)

Abstract

Abstract Viral infections in the lung are an important cause of morbidity and mortality in humans worldwide. In order to design strategies for vaccination and therapy, we need to understand the molecular mechanisms that initiate and regulate effective antiviral immune responses in the lung. This requires animal models in which in vitro mechanistic studies can be correlated with infections in vivo. We study rat coronavirus (RCoV) infection in rats and cultures of primary differentiated rat alveolar epithelial cells as a model for the early events in respiratory coronavirus pathogenesis. Intratracheal inoculation of adult rats with RCoV resulted in infection of the lung, primarily in alveolar type I cells. Infection caused transient weight loss and focal lesions and recruitment of neutrophils in the lung, followed by clearance of virus and resolution of inflammation. Thus, adult rats mounted an effective innate immune response to RCoV infection in the lung. In agreement, in primary cultures of differentiated rat alvoelar type I cells, RCoV replicated and induced expression of neutrophil chemotactic CXC chemokines. This in vitro model will elucidate the molecular interactions between RCoV and alveolar epithelial cells that initiate and regulate the innate antiviral immune response in the lung. This work was supported by NIH grants AI-059576 and HL-029891, and NCRR/NIH grant P20 RR015587.