Evidence map›Paper›PMID 25409547›Full record

ArticleNature communications2014

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 and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

129 citing papers in PubMed.

  1. Article
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  4. Review
  5. Article
  6. Article
  7. Article
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  9. Influenza NS1 drives NEmerging microbes & infections · 2025
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  10. Avian influenza overview September-November 2025.EFSA journal. European Food Safety Authority · 2025
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Wenjun Song1] State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China [2] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Pui Wang1] State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China [2] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Bobo Wing-Yee MokState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Siu-Ying LauState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Xiaofeng HuangState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Wai-Lan WuState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Min ZhengState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Xi WenState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
Shigui Yang1] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China [2] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Yu Chen1] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China [2] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Lanjuan Li1] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China [2] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Kwok-Yung Yuen1] State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China [2] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
Honglin Chen1] State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China [2] The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AnimalsBase SequenceDogsHEK293 CellsHumansInfluenza A Virus, H3N2 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza A Virus, H7N9 SubtypeMiceMolecular Sequence DataRNA-Dependent RNA PolymeraseViral ProteinsVirus ReplicationPB2 protein, Influenzavirus ARNA-Dependent RNA PolymeraseViral Proteins

Identifiers

PMID25409547
PMCPMC4263149

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.