A/swine/Fujian/1/2001 (FJ1) and A/Duck/Zhejiang/52/2000 (DK52) are H5N1 influenza viruses that are lethal in chickens. However, in mice, FJ1 is highly pathogenic, whereas DK52 cannot replicate at all. In this study, we used reverse genetics to demonstrate that amino acid residues at position 54 of polymerase acidic protein (PA) and position 26 of ion channel protein M2 of FJ1 and DK52 are important determinants for replication in mice. In addition, we prove that M2 and PA proteins contribute to the replication of H5N1 viruses in mice.
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