The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication

Wenjun Song, Pui Wang, Bobo Wing-Yee Mok, Siu-Ying Lau, Xiaofeng Huang, Wai-Lan Wu, Min Zheng, Xi Wen, Shigui Yang, Yu Chen, Lanjuan Li, Kwok-Yung Yuen () and Honglin Chen ()
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Wenjun Song: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Pui Wang: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Bobo Wing-Yee Mok: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Siu-Ying Lau: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Xiaofeng Huang: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Wai-Lan Wu: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Min Zheng: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Xi Wen: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Shigui Yang: The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
Yu Chen: The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
Lanjuan Li: The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
Kwok-Yung Yuen: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
Honglin Chen: State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Host-adaptive strategies, such as the E627K substitution in the PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970. Polymerase complexes containing PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.

Date: 2014
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DOI: 10.1038/ncomms6509

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