Aldose reductase AKR1B1,classified within the aldo-keto reductase family,is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes.In order to investigate the specific mechanism by which aldose reductase AKR1B1 regulates influenza virus replication,knockdown the expression of AKR1B1 gene in A549 cells was performed by siRNA interference.RT-qPCR showed that si_AKR1B1_671 could effectively reduce the mRNA level of AKR1B1 gene in A549 cells,which decreased by 95.62%(P<0.001)compared with the control group.Western blot showed that si_AKR1B1_671 could significantly reduce the expression of AKR1B1 in A549 cells and did not affect cell viability.The results of plaque assay showed that knockdown AKR1B1 significantly increased the viral titer of influenza virus WSN.Virus titers of 24hpi and 48hpi were increased by 4.39 times and 5.53 times,respectively.The outcome of western blot showed that knockdown AKR1B1 expression significantly increased intracellular viral protein content compared with the control group.Furthermore,overexpression of AKR1B1 could significantly reduce influenza virus WSN titer by plaque assay.Influenza virus titers decreased by 62.59%(P<0.01)and 82.78%(P<0.001)at 24 hours and 48 hours after infection compared with control group,respectively.The results of the polymerase activity of influenza virus showed that overexpression of AKR1B1 decreased influenza virus polymerase activity by 26.24%(P<0.001).In conclusion,the aldose reductase AKR1B1 may inhibit influenza virus replication by suppressing influenza virus polymerase activity.This study preliminarily investigated the molecular mechanism of host factor AKR1B1 involved in influenza virus replication and provided experimental data for further understanding of the regulation of influenza virus replication.