RNF213 Is an Interferon-Stimulated Gene That Targets Influenza A Virus NP and Activates MDA5 to Restrict Infection.

Haoning Li, Yuying Zhang, Jingjing Wang, Qianqian Zhang, Hailiang Sun, Fanhua Wei

Abstract read

In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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

6 authors.

Haoning LiCollege of Animal Science and Technology, Ningxia University, Yinchuan, China.

Yuying ZhangSchool of Biological Science and Technology, University of Jinan, Jinan, China.

Jingjing WangCollege of Animal Science and Technology, Ningxia University, Yinchuan, China.

Qianqian ZhangCollege of Animal Science and Technology, Ningxia University, Yinchuan, China.

Hailiang SunCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Fanhua WeiCollege of Animal Science and Technology, Ningxia University, Yinchuan, China.ORCID https://orcid.org/0000-0002-2997-922X

Funding

National Natural Science Foundation of China 32372994National Natural Science Foundation of China 32473004

6 · The paper itself

Abstract

Influenza A virus (IAV) infection induces a type I interferon (IFN) response in host cells, which exerts antiviral effects by upregulating interferon-stimulated genes (ISGs). However, the ISG response to IAV remains incompletely understood. Here, we systematically identify antiviral ISGs in A549 cells following type I and type II IFN treatment. We demonstrate that ring finger protein 213 (RNF213) strongly inhibits IAV replication in vitro. Notably, RNF213 knockout (KO) mice exhibit heightened susceptibility to IAV infection, with exacerbated disease severity. Mechanistically, RNF213, which is induced by both IFN signaling and IAV infection, amplifies IFN production by enhancing melanoma-differentiation-associated gene 5 (MDA5) signaling. We further show that RNF213 interacts with MDA5 via its AAA+ ATPase and E3 ligase domains, promoting K63-linked polyubiquitination of MDA5 at Lys137 and Lys743. Additionally, RNF213 mediates K48-linked polyubiquitination of viral nucleoprotein (NP), targeting it for proteasomal degradation. Our findings identify RNF213 as a critical antiviral ISG that bridges innate immune activation and direct viral restriction. Our study reveals a dual mechanism of RNF213 in antiviral immunity, highlighting its potential as a therapeutic target against influenza.

Indexed as

Influenza A virusInfluenza, HumanInterferon-Induced Helicase, IFIH1InterferonsRNA-Binding ProteinsUbiquitin-Protein LigasesA549 CellsAnimalsHumansInterferon Type IMiceMice, KnockoutNucleocapsid ProteinsUbiquitinationVirus ReplicationIFIH1 protein, humanInterferon-Induced Helicase, IFIH1InterferonsInterferon Type INP protein, Influenza A virusNucleocapsid ProteinsRNA-Binding ProteinsUbiquitin-Protein Ligasesinfluenza virusinterferoninterferon‐stimulated genesMDA5RNF213

Identifiers

PMID41849692

DOI10.1002/advs.202511012

PMCPMC13588011

What OpenQuestion holds

Textmetadata

Read underepoch 390

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.