RESEARCH ARTICLE Infection with a Mouse-Adapted Strain of the 2009 Pandemic Virus Causes a Highly Severe Disease Associated with an Impaired T Cell Response

Despite a relatively low fatality rate, the 2009 H1N1 pandemic virus differed from other sea-sonal viruses in that it caused mortality and severe pneumonia in the young and middle-aged population (18–59 years old). The mechanisms underlying this increased disease severity are still poorly understood. In this study, a human isolate of the 2009 H1N1 pan-demic virus was adapted to the mouse (MAp2009). The pathogenicity of the MAp2009 virus and the host immune responses were evaluated in the mouse model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 virus reached consis-tently higher titers in the lungs over 14 days compared to the PR8 virus, and caused severe disease associated with high morbidity and 85%mortality rate, contrasting with the 0% death rate in the PR8 group. During the early phase of infection, both viruses induced simi-lar pathology in the lungs. However, MAp2009-induced lung inflammation was sustained until the end of the study (day 14), while there was no sign of inflammation in the PR8-infected group by day 10. Furthermore, at day 3 post-infection, MAp2009 induced up to 10-to 40-fold more cytokine and chemokine gene expression, respectively. More importantly