Influenza Pathogenesis in Genetically Defined Resistant and Susceptible Murine Strains



The murine infection model is a cornerstone for influenza virus research and includes aspects such as disease pathogenesis, immunobiology, and vaccine and antiviral drug development. One compelling feature of the murine model is the availability of inbred mouse strains, each with a unique genetic makeup and potential for variable responses to influenza infection. Using highly controlled infection studies, the response to influenza virus infection is classified on a spectrum from susceptible to resistant, reflecting severe morbidity and high mortality, to limited or no morbidity and no mortality. Although there have been a variety of studies establishing disparate pathogenesis amongst various murine strains, thus far, there is no consensus regarding the determinants of the outcome of infection. The goal of this review is to explore and discuss the differences in pathogenesis, as well as the innate and adaptive immune responses to influenza infection that have been described in susceptible and resistant mouse strains. Understanding how host genetics influences the response to influenza infection provides valuable insight into the variable responses seen in vaccine or drug efficacy studies, as well as indicates possible mechanisms contributing to increased disease severity in humans infected with influenza virus with no known risk factors.