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

Suli Liu,Wenfei Zhu,Zhaomin Feng,Rongbao Gao,Junfeng Guo,Xiyan Li,Jia Liu,Dayan Wang,Yuelong Shu

doi:10.1038/s41426-018-0073-6

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.

Highlights

Introduction InfluenzaA virus infection usually causes substantial mortality and morbidity
As the genetic mixing vessels for avian and human influenza viruses, pigs are the intermediate hosts for the adaption and pathogenicity of avian influenza viruses and, are potentially capable of initiating pandemics in humans[1]
Considering the possibility of Eurasian avian-like H1N1 (EA H1N1) SIVs causing a future human influenza pandemic and the great significance of the 701N mutation in host adaptation, our study focused on the effects of the substitution of the mammalian signature 701N in the PB2 protein on this newly emerged reassortant (A/Hunan/42443/2015(H1N1), HuN EAH1N1, accession nos

Summary

Introduction

Introduction InfluenzaA virus infection usually causes substantial mortality and morbidity. The EA H1N1 SIVs were first detected in 19792 and have caused several human infections in Europe and Asia since [3,4,5,6,7,8,9]. With the increased binding affinity to human-type receptors and the enhanced transmissibility in mammals, EA H1N1 virus has become one of the candidates with the greatest likelihood to raise pandemics[1,10,11]. The D701N mutation in the PB2 protein was originally observed upon the adaption of H3N2, H5N1, and H7N7 viruses in mice[16,17,18] and was associated with enhanced viral polymerase activity and pathogenicity[16,17,18,19,20]. Increased interaction between 701N and cellular importin-α, a component of the nuclear import machinery, was believed to contribute to adaptation, resulting in enhanced nuclear import of vRNPs21,22

Methods

Results

Conclusion