Evidence map›Paper›PMID 40920865›Full record

ArticlePLoS pathogens2025

N460S in PB2 and I163T in nucleoprotein synergistically enhance the viral replication and pathogenicity of influenza B virus.

Yang Wang, Yu Gao, Tianxin Ma, Yuting Ye, Chenyang Cao, Binqian Zou, Sulan Ye, Qingsheng Huang, Chunguang Yang, Shengfeng Li and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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

15 authors.

Yang WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.ORCID 0000-0002-6527-864X
Yu GaoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Tianxin MaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Yuting YeState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Chenyang CaoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Binqian ZouState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Sulan YeState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Qingsheng HuangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Chunguang YangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Shengfeng LiState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Lixi LiangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Hongxuan ZhouState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Zhiqi ZengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Zifeng YangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Weiqi PanState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Funding

National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaScience and Technology Development Fund of Macau SARState Key Laboratory of Respiratory Disease
6 · The paper itself

Abstract

Influenza B viruses (IBVs), though often overshadowed by influenza A viruses (IAVs), remain a significant global public health concern, particularly during seasons when they predominate. However, the molecular mechanisms underlying IBV pathogenicity remain largely unknown. In this study, we identified two amino acid substitutions, PB2-N460S and NP-I163T, from IBV clinical isolates with distinct replication and pathogenicity profiles. Using reverse genetics, we generated recombinant IBV viruses to evaluate the impact of these substitutions. In vitro and in vivo infections revealed that viral replication and pathogenicity were not significantly affected by either substitution alone but were substantially enhanced when both substitutions occurred together. Lung transcriptomics in mice infected with virus containing PB2-N460S/NP-I163T substitutions showed heightened immune activation. This was characterized by upregulated transcription of antiviral and immune-related genes, contributing to excessive inflammation and severe disease outcomes. Mechanistic investigations demonstrated that each substitution independently increased protein expression and strengthened PB2-NP interactions. However, only the combined presence of PB2-N460S and NP-I163T significantly enhanced polymerase activity. Structural modeling indicated that PB2-460 residue is positioned at the PB2-NP interface, while NP-163 site resides distally, suggesting an indirect functional interplay. These findings provide new insights into the molecular determinants of IBV pathogenesis, highlighting the synergistic effect of PB2-N460S and NP-I163T in enhancing viral fitness and worsening disease outcomes.

Indexed as

Influenza B virusNucleoproteinsOrthomyxoviridae InfectionsRNA-Dependent RNA PolymeraseViral ProteinsVirus ReplicationAmino Acid SubstitutionAnimalsDogsFemaleHumansInfluenza, HumanMiceMice, Inbred BALB CVirulenceNucleoproteinsPB2 protein, influenza virusRNA-Dependent RNA PolymeraseViral Proteins

Identifiers

PMID40920865
PMCPMC12431660

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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.