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The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication
Wenjun Song1, 2, n1
Pui Wang1, 2, n1
Bobo Wing-Yee Mok1,
Siu-Ying Lau1,
Xiaofeng Huang1,
Wai-Lan Wu1,
Min Zheng1,
Xi Wen1,
Shigui Yang2, 3,
Yu Chen2, 3,
Lanjuan Li2, 3,
Kwok-Yung Yuen1, 2,
Honglin Chen1, 2,
Nature Communications
5,
Article number:
5509
doi:10.1038/ncomms6509
Received
23 May 2014
Accepted
07 October 2014
Published
20 November 2014
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.
open article
Wenjun Song1, 2, n1
Pui Wang1, 2, n1
Bobo Wing-Yee Mok1,
Siu-Ying Lau1,
Xiaofeng Huang1,
Wai-Lan Wu1,
Min Zheng1,
Xi Wen1,
Shigui Yang2, 3,
Yu Chen2, 3,
Lanjuan Li2, 3,
Kwok-Yung Yuen1, 2,
Honglin Chen1, 2,
Nature Communications
5,
Article number:
5509
doi:10.1038/ncomms6509
Received
23 May 2014
Accepted
07 October 2014
Published
20 November 2014
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.
open article
