UNASSIGNED: @entity1 alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. In this study we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by @entity281 . However, there is significant variation in the cellular permissiveness to @entity281 among different donors. AECs from @entity28 donors appear to be more susceptible to @entity281 , whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single @entity3689 residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of @entity1 lung primary cells and the integrity of the alveolar epithelial barrier to @entity683 . Further elucidation of the mechanism of increased susceptibility of AECs from @entity28 subjects may facilitate the development of novel protection strategies against @entity281 . IMPORTANCE: Disease susceptibility of @entity683 is determined by host and viral factors. @entity1 alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that @entity28 might be a risk factor for increased susceptibility to @entity683 . We also compared the infection of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary @entity1 AECs can serve as a convenient and powerful model to investigate the mechanism of @entity683 induced @entity651 and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic @entity281 .

Differential susceptibility of XXXX lung primary cells to H1N1 @entity683 viruses.

@entity1 :: ('9606', 'Species') :: ['human', 'Human'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obese', 'obesity'] @entity651 :: ('MESH:D055370', 'Disease') :: ['lung injury'] @entity281 :: ('MESH:D007239', 'Disease') :: ['influenza infection', 'H1N1pdm09 infection'] @entity683 :: ('MESH:D007251', 'Disease') :: ['influenza'] @entity3689 :: ('D000596', 'Chemical') :: ['amino acid']
@entity1 :: (9606,Species) :: ['human']
