Evidence map›Paper›PMID 41211819›Full record

ArticlemBio2025

Human-specific activation of the DUX4-SLC34A2 axis by herpesviruses suppresses antiviral innate immunity.

Ming Gao, Xi Cheng, Chuchu Zhang, Jiali Ma, Xuezhang Tian, Shaowei Wang, Xiaoyu Xie, Yunhong Zhong, Siyuan Wang, Pinghui Feng and 1 more

Abstract read
In one paragraph

Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Ming GaoState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.ORCID 0009-0007-8974-5592
Xi ChengState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Chuchu ZhangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Jiali MaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Xuezhang TianState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Shaowei WangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Xiaoyu XieDepartment of Colorectal and Anal Surgery, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yunhong ZhongState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Siyuan WangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Pinghui FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
Junjie ZhangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.ORCID 0000-0003-3812-3850

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Viral pathogens employ diverse strategies to antagonize host antiviral innate immune defenses. However, the human-specific nature of viral immune evasion mechanisms remains poorly understood. Here, we report that herpesvirus infection selectively activates the embryonic transcription factor DUX4 in human but not murine cells. DUX4 drives the expression of the phosphate transporter SLC34A2, which plays a critical role in suppressing antiviral innate immunity. Mechanistically, SLC34A2 increases intracellular phosphate levels, thereby suppressing the activity of multiple immune and stress-related kinases, including TBK1. Genetic disruption of DUX4 or SLC34A2 restores innate immune activation and enhances interferon responses. Our findings reveal a previously unrecognized, phosphate-mediated immunosuppressive mechanism and define a human-specific transcriptional circuit exploited by herpesviruses to antagonize innate immunity.IMPORTANCEHerpesviruses are notorious for their ability to evade host immune responses, yet the mechanisms underlying human-specific immune evasion remain poorly understood. This study identifies a previously unrecognized viral immune evasion strategy by which herpesviruses suppress antiviral immunity in human cells but not murine cells. We demonstrate that herpesvirus infection induces the expression of the embryonic transcription factor DUX4, which subsequently activates its downstream target, SLC34A2, a phosphate transporter. DUX4-SLC34A2 activation reprograms infected cells toward an embryonic-like transcriptional profile, creating an environment conducive to viral replication. Importantly, we show that SLC34A2 increases intracellular phosphate levels, thereby suppressing the activity of multiple immune and stress-related kinases, including TBK1. Our findings reveal a previously unrecognized phosphate-mediated regulation of antiviral immunity, providing insights into viral-host interactions and highlighting therapeutic targets for enhancing antiviral defense.

Indexed as

HerpesviridaeHomeodomain ProteinsImmune EvasionImmunity, InnateAnimalsCell LineHEK293 CellsHost-Pathogen InteractionsHumansMicePhosphatesProtein Serine-Threonine KinasesHomeodomain ProteinsPhosphatesProtein Serine-Threonine Kinasesantiviral innate immunityherpesvirusimmune evasionphosphate

Identifiers

PMID41211819
PMCPMC12691587

What Socratic 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 Socratic graph.