Evidence map›Paper›PMID 41422038›Full record

ArticleNature communications2025

Emergence of mammalian-adaptive PB2 mutations enhances polymerase activity and pathogenicity of cattle-derived H5N1 influenza A virus.

Lei Zhang, Yuerong Lai, Yingzi Cui, Qiuxian Yang, Yuekun Shao, Shenyang Ding, Haojie Wang, Liang Wang, George Fu Gao, Tao Deng

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

10 authors.

Lei Zhang *Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-9269-9706
Yuerong Lai *Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Yingzi Cui *State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Qiuxian Yang *Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Yuekun ShaoLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Shenyang DingLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Haojie WangLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Liang WangLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-7897-8581
George Fu GaoLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.ORCID http://orcid.org/0000-0002-3869-615X
Tao DengLaboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. dengt@im.ac.cn.ORCID http://orcid.org/0000-0002-8303-0891

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82472248
6 · The paper itself

Abstract

Highly pathogenic avian influenza H5N1 poses an increasing public health risk, particularly following its spillover into dairy cows and associated human infections in the U.S. since March 2024. Here, we systematically identified critical PB2 mutations emerged during avian-to-cattle transmission and subsequent adaptation in cattle, notably PB2 M631L, which conferred pathogenicity in mice comparable to the well-characterized PB2 E627K mutation. Retrospective analysis reveals that PB2 631L also circulated in avian and human H5N1 strains during the 2013-2014 outbreaks in Cambodia and Vietnam. Additional adaptive mutations include established markers (E627K, Q591R, D701N), and novel variants (I647V, G685R, K736R). These mutations enhance polymerase activity by improving the utilization of both bovine and human ANP32A proteins, thereby increasing viral fitness and pathogenicity in mammals. The convergence of these adaptations highlights the elevated zoonotic risk of cattle-adapted H5N1 viruses and underscores the urgent need for heightened surveillance across avian and mammalian hosts.

Indexed as

Cattle DiseasesInfluenza A Virus, H5N1 SubtypeOrthomyxoviridae InfectionsRNA-Dependent RNA PolymeraseViral ProteinsAnimalsCattleFemaleHumansInfluenza, HumanInfluenza in BirdsMiceMutationVirulencePB2 protein, Influenzavirus ARNA-Dependent RNA PolymeraseViral Proteins

Identifiers

PMID41422038
PMCPMC12847931

What OpenQuestion holds

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Registered trials

None linked

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.