Evidence map›Paper›PMID 35173169›Full record

ArticleNature communications2022

Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection.

Saravanan Gunaseelan, Mohammed Zacky Ariffin, Sanjay Khanna, Mong How Ooi, David Perera, Justin Jang Hann Chu, John Jia En Chua

RetractedErratum issuedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Saravanan GunaseelanDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Mohammed Zacky AriffinDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-6228-3830
Sanjay KhannaDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-7304-6259
Mong How OoiDepartment of Paediatrics, Sarawak General Hospital, Kuching, Sarawak, Malaysia.
David PereraInstitute of Health and Community Medicine, Universiti Malaysia Sarawak, Kota Samarahan, Sarawak, Malaysia.
Justin Jang Hann ChuDepartment of Microbiology and Immunology, National University of Singapore, Singapore, 117597, Singapore. miccjh@nus.edu.sg.ORCID http://orcid.org/0000-0002-1673-6819
John Jia En ChuaDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. phsjcje@nus.edu.sg.ORCID http://orcid.org/0000-0002-5615-1014
National University of Singapore · SGAgency for Science, Technology and Research · SGSarawak General Hospital · MYUniversiti Malaysia Sarawak · MY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.

Indexed as

AnimalsAstrocytesCell LineCentral Nervous System DiseasesChemokine CXCL1Disease Models, AnimalEnterovirus A, HumanFemaleHand, Foot and Mouth DiseaseHEK293 CellsHumansMAP Kinase Signaling SystemMiceMice, Inbred BALB CPyrimidinesRatsChemokine CXCL1CXCL1 protein, humanCXCR2 protein, humanN-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamidePyrimidinesReceptors, Interleukin-8BSulfonamides

Identifiers

PMID35173169
PMCPMC8850555
OpenAlexW4212803316

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.