Figure 8: Model of adaptive mutations contributing to the replication of avian H5N1 isolates in human cells.
From: Adaptive mutations in NEP compensate for defective H5N1 RNA replication in cultured human cells
Our results suggest that cRNPs can be formed in human cells infected with AvianPr. Nevertheless, viral vRNP replication seems to be impaired, possible by premature degradation of cRNA. This defect in viral replication is not observed in cells infected with AvianPr PB2-E627K, indicating the single adaptive mutation E627K in PB2 is sufficient to overcome this defect. However, vRNPs are also efficiently generated in cells infected with human-derived H5N1 strains, such as KAN-1, lacking this human signature in PB2. In this case, the block in vRNP synthesis was overcome by a single adaptive mutation (M16I) in NEP of KAN-1 that increased the activity of this protein to enhance viral replication.
