PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses.

Chencheng Xiao,Yuandi Yu,Zhangyong Ning,Ming Liao,Wenjun Ma,Xu Zhang,Qian Li,Yijun Wen,Zaoyue Zhang,Pingsheng Hu,Shukai Liu,Lihong Huang,Huanan Li,Zhaoyong Zeng,Yi Zheng,Na Sun,Wenbao Qi,Yaling Li

doi:10.1038/srep19474

Chencheng Xiao, Yuandi Yu + Show 16 more

Open Access

https://doi.org/10.1038/srep19474

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Abstract

Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts.

Highlights

Influenza A virus (IAV) is an important zoonotic pathogen that infects mammals and birds and induces seasonal influenza epidemics and pandemics in humans
No virus was detected in these tissues, indicating that the fatal H7N9, H10N8 and H9N2 viruses did not induce a systematic infection which is often observed with H5N1 influenza viruses[37]
The severe infection was consistent with our mouse experiments of both human-origin H7N9 and H10N8 viruses that showed high virulence and efficient virus replication in mice

Summary

Introduction

Influenza A virus (IAV) is an important zoonotic pathogen that infects mammals and birds and induces seasonal influenza epidemics and pandemics in humans. One well-characterized mutation in PB2 is the glutamate change to lysine at position 627 (E627K)[22] that results in efficient virus replication in mammalian cells and enhanced virulence in mammals[23,24,25]. This mutation is found in several subtypes of AIVs including H5N1, H7N7, and H9N2 viruses. Another well-known substitution D701N in PB2 is primarily found in a duck H5N1 virus that was highly pathogenic to mice[26,27]. The single substitution A588V in PB2 enhanced polymerase activity, virus replication, and virulence of avian influenza H10N8, H7N9, and H9N2 virus isolates

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