Evidence map›Paper›PMID 38593069›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses.

Linjuan Wu, Liming Zhang, Shengyong Feng, Lu Chen, Cai Lin, Gang Wang, Yibin Zhu, Penghua Wang, Gong Cheng

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Insights into SARS-CoV-2 replication controlActa pharmaceutica Sinica. B · 2026
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  11. Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025
    Review
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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

9 authors at 3 institutions in 2 countries.

Linjuan WuNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Liming ZhangNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.ORCID 0000-0002-3500-9043
Shengyong FengNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Lu ChenNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.ORCID 0000-0003-4443-5586
Cai LinInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen 518000, China.
Gang WangNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Yibin ZhuNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Penghua WangDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030.
Gong ChengNew Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Peking University · CNShenzhen Bay Laboratory · CNUConn Health · US

Funding

National Key Research and Development Plan of ChinaNational Natural Science Foundation of ChinaShenzhen San-Ming Project for Prevention and Research on Vector-borne Diseases
6 · The paper itself

Abstract

Mosquito-borne flaviviruses such as dengue (DENV) and Zika (ZIKV) cause hundreds of millions of infections annually. The single-stranded RNA genome of flaviviruses is translated into a polyprotein, which is cleaved equally into individual functional proteins. While structural proteins are packaged into progeny virions and released, most of the nonstructural proteins remain intracellular and could become cytotoxic if accumulated over time. However, the mechanism by which nonstructural proteins are maintained at the levels optimal for cellular fitness and viral replication remains unknown. Here, we identified that the ubiquitin E3 ligase HRD1 is essential for flaviviruses infections in both mammalian hosts and mosquitoes. HRD1 directly interacts with flavivirus NS4A and ubiquitylates a conserved lysine residue for ER-associated degradation. This mechanism avoids excessive accumulation of NS4A, which otherwise interrupts the expression of processed flavivirus proteins in the ER. Furthermore, a small-molecule inhibitor of HRD1 named LS-102 effectively interrupts DENV2 infection in both mice and

Indexed as

AedesFlavivirusFlavivirus InfectionsZika VirusZika Virus InfectionAnimalsLigasesMammalsMiceUbiquitinViral ProteinsLigasesUbiquitinViral ProteinsER-associated degradationflavivirusHRD1mosquitoNS4A

Identifiers

PMID38593069
PMCPMC11032495
OpenAlexW4394597756

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.