Evidence map›Paper›PMID 34285233›Full record

ArticleNature communications2021

MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes.

Xiaoman Liu, Fengwen Xu, Lili Ren, Fei Zhao, Yu Huang, Liang Wei, Yingying Wang, Conghui Wang, Zhangling Fan, Shan Mei and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
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

59 citing papers in PubMed, 89 citations in OpenAlex.

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  5. NIBV Induces Incomplete Autophagy via AMPK-TFEB, Causing Kidney Injury in Chicks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  8. Article
  9. Article
  10. Review
  11. MARCH E3 Ligases: Understudied Regulators of Pulmonary Immune Function.Journal of respiratory biology and translational medicine · 2026
    Article
  12. Carbon Quantum Dots Assisted Virus Tracking: From Skin to Brain.Advanced materials (Deerfield Beach, Fla.) · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. ARRDC4-mediated glycolysis enhances innate immunity to influenza A virus through fructose-1,6-bisphosphate.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Article
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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

16 authors at 3 institutions in 2 countries.

Xiaoman Liu *NHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Fengwen Xu *NHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Lili Ren *NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Fei ZhaoNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yu HuangNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Liang WeiNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yingying WangNHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Conghui WangNHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Zhangling FanNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shan MeiNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jingdong SongNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Zhendong ZhaoNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shan CenInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chen LiangMcGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.
Jianwei WangNHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. wangjw28@163.com.ORCID 0000-0002-1116-4559
Fei GuoNHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. guofei@ipb.pumc.edu.cn.ORCID 0000-0003-3500-1006
Chinese Academy of Medical Sciences & Peking Union Medical College · CNJewish General Hospital · CANational Institute for Viral Disease Control and Prevention · CN

Funding

CIHR CCI-132561
6 · The paper itself

Abstract

The membrane-associated RING-CH (MARCH) proteins are E3 ligases that regulate the stability of various cellular membrane proteins. MARCH8 has been reported to inhibit the infection of HIV-1 and a few other viruses, thus plays an important role in host antiviral defense. However, the antiviral spectrum and the underlying mechanisms of MARCH8 are incompletely defined. Here, we demonstrate that MARCH8 profoundly inhibits influenza A virus (IAV) replication both in vitro and in mice. Mechanistically, MARCH8 suppresses IAV release through redirecting viral M2 protein from the plasma membrane to lysosomes for degradation. Specifically, MARCH8 catalyzes the K63-linked polyubiquitination of M2 at lysine residue 78 (K78). A recombinant A/Puerto Rico/8/34 virus carrying the K78R M2 protein shows greater replication and more severe pathogenicity in cells and mice. More importantly, we found that the M2 protein of the H1N1 IAV has evolved to acquire non-lysine amino acids at positions 78/79 to resist MARCH8-mediated ubiquitination and degradation. Together, our data support the important role of MARCH8 in host anti-IAV intrinsic immune defense by targeting M2, and suggest the inhibitory pressure of MARCH8 on H1N1 IAV transmission in the human population.

Indexed as

A549 CellsAmino Acid SequenceAnimalsDisease Models, AnimalDogsGene Knockdown TechniquesHEK293 CellsHeLa CellsHemagglutinin Glycoproteins, Influenza VirusHost Microbial InteractionsHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanLysineLysosomesMadin Darby Canine Kidney CellsHemagglutinin Glycoproteins, Influenza VirusLysineM2 protein, Influenza A virusMarch8 protein, mouseMARCHF8 protein, humanUbiquitin-Protein LigasesViral Matrix ProteinsViroporin Proteins

Identifiers

PMID34285233
PMCPMC8292393
OpenAlexW3183546851

What OpenQuestion holds

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LicenceCC BY
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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.