Evidence map›Paper›PMID 42420525›Full record

ArticleNature immunology2026

ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.

Jing-Yu Weng, Xin-Xing Chen, Hui-Er Ye, Ying-Ying Zeng, Wan-Li Liang, Yin-Ci Zhang, Xin-Yu Zong, Chang-Yu Yan, Yue Ye, Yan-Ping Wu and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Jing-Yu Weng *State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Xin-Xing Chen *State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Hui-Er YeState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Ying-Ying ZengState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Wan-Li LiangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Yin-Ci ZhangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Xin-Yu ZongState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Chang-Yu YanState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Yue YeState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Yan-Ping WuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Wan-Yang SunState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-4439-967X
Wen-Jun DuanState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Lei LiangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Yuqi YanDepartment of Clinical Laboratory Medicine, The First Clinical Medical College, Jinan University, Guangzhou, China.
Yun-Feng CaoShanghai Institute for Biomedical and Pharmaceutical Technologies, National Health Commission Key Laboratory of Reproduction Regulation, Shanghai, China.
Yi DaiState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Hiroshi KuriharaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Hao GaoState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China.
Shu-Hua OuyangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China. shouyang@jnu.edu.cn.ORCID http://orcid.org/0009-0008-2000-5454
Yi-Fang LiState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China. liyifang706@jnu.edu.cn.ORCID http://orcid.org/0000-0002-3356-3702
Rong-Rong HeState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China. rongronghe@jnu.edu.cn.ORCID http://orcid.org/0000-0001-5505-5672

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82174054National Natural Science Foundation of China (National Science Foundation of China) 82321004National Natural Science Foundation of China (National Science Foundation of China) 82474157
6 · The paper itself

Abstract

Viral infections trigger cellular stress responses, and host stress proteins play key roles in antiviral defense. Here we identify stress-responsive protein arachidonate lipoxygenase-15 (ALOX15) is a critical component of mitochondrial antiviral innate immunity. Loss of Alox15 impairs mitochondrial antiviral signaling (MAVS)-mediated type I interferon production, resulting in increased susceptibility to influenza virus, an effect reversed by adeno-associated virus-mediated lung delivery of Alox15. ALOX15 translocates to mitochondria in response to H1N1 and other RNA viruses (H3N2 and human coronavirus-229E), independent of its enzymatic activity. This mitochondrial localization is also strikingly observed in peripheral blood mononuclear cells from influenza-infected individuals. Mechanistically, ALOX15 is recruited to mitochondria by polymerized MAVS, displacing the deubiquitinase USP19 and sustaining MAVS K63-linked ubiquitination and aggregation. Leveraging these insights, we developed a synergistic ALOX15 regulation-based therapeutic strategy for influenza infection by combining the ALOX15 transcriptional activator songorine with its enzymatic inhibitor PD146176. Together, our findings establish ALOX15 as an essential component of mitochondrial antiviral immunity and a promising host-directed target for antiviral therapy.

Indexed as

Arachidonate 15-LipoxygenaseInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMitochondriaOrthomyxoviridae InfectionsAdaptor Proteins, Signal TransducingAnimalsArachidonate 12-LipoxygenaseHost-Directed TherapyHumansImmunity, InnateInfluenza A Virus, H3N2 SubtypeInterferon Type IMiceMice, KnockoutSignal TransductionAdaptor Proteins, Signal TransducingAlox15 protein, mouseArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseInterferon Type IMAVS protein, human

Identifiers

PMID42420525

What Socratic holds

Textmetadata
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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 Socratic graph.