The adaptation of avian influenza viruses to the respiratory epithelium of pigs

Pig is an important host for influenza A viruses and may play a crucial role in the interspecies transmission. To analyze the infection by influenza viruses, we have established precision-cut lung slices (PCLS) from the porcine lung as a culture system for differentiated respiratory epithelial cells. In PCLS, the differentiated epithelial cells are maintained in their original setting. As differentiated respiratory epithelial cells are the primary target cells for influenza virus infections, PCLS provide an interesting system to analyze the adaptation of avian influenza viruses to the respiratory epithelium of pigs. Avian influenza viruses of the H9N2 subtype were subjected to several passages in PCLS. Adaptation of the avian viruses to growth in porcine cells was evident in a shortening of the growth cycle. Sequence analysis revealed that few amino acid changes occurred during the different virus passages. The importance of the individual mutations is currently analyzed by generating recombinant viruses that contain the respective mutated proteins. Our study will help to understand the processes involved in the adaptation of H9N2 influenza viruses to new hosts.