FIG 6.

Cooperative effects of PA mutations on clade 2.2.1 polymerase activity in human and avian cells. (A to C) Polymerase activity of contemporary EG13 viruses, each carrying the indicated PA reverse mutation, singly or in combination, measured by minigenome assays in human 293T cells at 33°C (A) and 37°C (B) and in avian DF-1 cells at 37°C (C). The data are expressed relative to the results for wild-type EG13. (D to F) Polymerase activity of ancestral D1 viruses, each carrying the indicated PA forward mutation, singly or in combination, measured by minigenome assays in human 293T cells at 33°C (D) and 37°C (E) and in avian DF-1 cells at 37°C (F). The data are expressed relative to the results for wild-type D1. Each data point is the mean ± SD from five independent experiments. Asterisks indicate a P value of <0.01.