In our study, we found that ShpK1 was upregulated during infection with the more mammalian-adapted DK1-like PB2 gene H9N2 AIV, while there was no significant change during infection with the F/98-like PB2 gene H9N2 AIV, and virus replication was inhibited by the SphK1. This evidence concerns the gene SPHK1 and infection.