UNASSIGNED: Despite a relatively low fatality rate, the 2009 H1N1 pandemic @entity778 differed from other seasonal viruses in that it caused mortality and severe @entity55 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 @entity1 isolate of the 2009 H1N1 pandemic @entity778 was adapted to the @entity19 (MAp2009). The pathogenicity of the MAp2009 @entity778 and the host immune responses were evaluated in the @entity19 model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 @entity778 reached consistently higher titers in the lungs over 14 days compared to the PR8 @entity778 , 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 similar pathology in the lungs. However, MAp2009-induced @entity55 was sustained until the end of the study (day 14), while there was no sign of @entity32 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, the numbers of CD4+ T cells and @entity778 -specific CD8+ T cells were significantly lower in the lungs of MAp2009-infected @entity19 compared to PR8-infected @entity19 . Interestingly, there was no difference in the number of dendritic cells in the lung and in the draining lymph node. Moreover, @entity19 infected with PR8 or MAp2009 had similar numbers of @entity13945 and @entity14013 -expressing T cells, suggesting that the impaired T cell response was not due to a lack of chemokine responsiveness or priming of T cells. This study demonstrates that a @entity19 -adapted @entity778 from an isolate of the 2009 pandemic @entity778 interferes with the adaptive immune response leading to a more severe disease.

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

@entity1 :: ('9606', 'Species') :: ['human'] @entity778 :: ('MESH:D015658', 'Disease') :: ['virus'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity13945 :: ('12774(Tax:10090)', 'Gene') :: ['CCR5'] @entity55 :: ('MESH:D011014', 'Disease') :: ['pneumonia', 'lung inflammation'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity14013 :: ('12766(Tax:10090)', 'Gene') :: ['CXCR3']
@entity19 :: (10090,Species) :: ['Mouse']
