Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses

Abstract

Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) have become predominant in pig populations in China and have recently been reported to have the most potential to raise the next pandemic in humans. The mutation D701N in the PB2 protein, which accounts for 31% of H1N1 SIVs, has previously been shown to contribute to the adaptation of the highly pathogenic H5N1 or H7N7 avian influenza viruses in mammals. However, little is known of the effects of this substitution on the EA H1N1 viruses. Herein, we investigated the contributions of 701N in the PB2 protein to an EA H1N1 SIV (A/Hunan/42443/2015(H1N1), HuN EA-H1N1), which had 701D in the PB2 protein. Our results found that viral polymerase activity, viral replication, and pathogenicity in mice were indeed enhanced due to the introduction of 701N into the PB2 protein, and the increased viral growth was partly mediated by the host factor importin-α7. Thus, substantial attention should be paid to the D701N mutation in pig populations.

These authors contributed equally: Suli Liu, Wenfei Zhu, Zhaomin Feng.

These authors contributed equally: Suli Liu, Wenfei Zhu, Zhaomin Feng.

Acknowledgements

This study was supported by the National Key Research and Development Program of China (2016YFC1200200 to Y.S.), the National Nature Science Foundation of China (81601758 to W.Z. and 81525017 to Y.S.), and the young scientist fund of Chinese Center for Disease Control and Prevention (2016A103 to W.Z.).

Author contributions

Y.S., D.W., and W.Z. designed the study; S.L., W.Z., Z.F., R.G., J.G., X.L., and J.L. performed the experiments; Y.S., S.L., and W.Z. analyzed data and discussed the results; S.L. wrote the manuscript; Y.S. and W.Z. revised the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Information accompanies this paper at (10.1038/s41426-018-0073-6).