Evidence map›Paper›PMID 42142585›Full record

ArticleThe Journal of biological chemistry2026

Molecular mechanism of 2',3'-cGAMP degradation by monkeypox virus poxin-schlafen protein.

Yunxiao Huang, Benzhen Duan, Yang Xiao, Xiaoman An, Hongyu Zhao, Jingwen Wang, Fenglei Du, Baoyu Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

8 authors.

Yunxiao HuangShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Benzhen DuanShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Yang XiaoShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Xiaoman AnShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Hongyu ZhaoShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Jingwen WangShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Fenglei DuShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Baoyu ZhaoShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: baoyuzhao@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The World Health Organization had declared the multiregional outbreak of monkeypox a global public health emergency twice since 2022. Poxin from orthopoxviruses degrades the second messenger 2',3'-cGAMP of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway to evade innate immune surveillance. Monkeypox virus (MPXV) poxin is fused to schlafen and the mechanism of how it catalyzes the degradation of 2',3'-cGAMP remains unclear. Here, we show that MPXV poxin-schlafen degrades 2',3'-cGAMP into Gp[2'-5']Ap[3'], suppressing interferon-β (IFN-β) induction mediated by the cGAS-STING pathway. The schlafen domain has no impact on the degradation of 2',3'-cGAMP mediated by the poxin domain. Crystal structures of MPXV poxin domain and its complex with Gp[2'-5']Ap[3'] reveal that 2',3'-cGAMP binds to a pocket formed by two monomers of the poxin dimer and induces closure of the pocket to trigger degradation. MPXV poxin exhibits a strict substrate specificity and does not degrade 3',3'-cGAMP, c-di-AMP, and c-di-GMP that also activate STING-mediated immune responses. These results unveil the molecular mechanism for 2',3'-cGAMP degradation by MPXV poxin-schlafen protein and provide the structural basis for the development of inhibitors against MPXV infection.

Indexed as

Monkeypox virusNucleotides, CyclicViral ProteinsAnimalscGAS-STING Signaling PathwayHumansModels, Molecularcyclic guanosine monophosphate-adenosine monophosphateNucleotides, CyclicViral Proteins2',3'-cGAMPcGAS-STING pathwayinnate immunitymonkeypox viruspoxin

Identifiers

PMID42142585
PMCPMC13273817

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.