Evidence map›Paper›PMID 29152574›Full record

ArticleScience advances2017

Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus.

Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao and 15 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
232citing papers in PubMed, 10 pooled it
32.4field-weighted citation impact, top 1% 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

232 citing papers in PubMed, 10 syntheses or guidelines pooled it, 389 citations in OpenAlex.

  1. Pooled it
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  3. Gut distress and interventionFrontiers in public health · 2023
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  11. Review
  12. Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  16. Article
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  18. Article
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172 more citing papers are in PubMed but not listed here.

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

25 authors at 4 institutions in 5 countries.

Jie ZhouState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.ORCID 0000-0002-2948-3873
Cun LiDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.ORCID 0000-0003-3003-0000
Guangyu ZhaoState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Hin ChuState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.
Dong WangDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Helen Hoi-Ning YanDepartment of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Vincent Kwok-Man PoonDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Lei WenDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Bosco Ho-Yin WongDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Xiaoyu ZhaoDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.ORCID 0000-0002-0347-9104
Man Chun ChiuDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.ORCID 0000-0001-9503-6396
Dong YangDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Yixin WangDepartment of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Rex K H Au-YeungDepartment of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.ORCID 0000-0002-3137-0886
Ivy Hau-Yee ChanDepartment of Surgery, Queen Mary Hospital, Hong Kong, China.
Shihui SunState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Jasper Fuk-Woo ChanState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.
Kelvin Kai-Wang ToState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.ORCID 0000-0002-1921-5824
Ziad A MemishMinistry of Health and College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
Victor M CormanInstitute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-3605-0136
Christian DrostenInstitute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ivan Fan-Ngai HungDepartment of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Yusen ZhouState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Suet Yi LeungDepartment of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Kwok-Yung YuenState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.ORCID 0000-0002-2948-3873
Queen Mary Hospital · CNInstitute of Microbiology · CNGerman Center for Infection Research · DEAlfaisal University · SA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.

Indexed as

AnimalsCaco-2 CellsCoronavirus InfectionsDipeptidyl Peptidase 4Epithelial CellsFecesFemaleHumansIntestine, SmallLungMiceMice, TransgenicMiddle East Respiratory Syndrome CoronavirusPantoprazoleRNA, ViralDipeptidyl Peptidase 4DPP4 protein, humanPantoprazoleRNA, Viral

Identifiers

PMID29152574
PMCPMC5687858
OpenAlexW2769543984

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.