Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
- PMID: 29152574
- PMCID: PMC5687858
- DOI: 10.1126/sciadv.aao4966
Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
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.
Figures
Similar articles
-
Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus.J Virol. 2019 Mar 5;93(6):e01818-18. doi: 10.1128/JVI.01818-18. Print 2019 Mar 15. J Virol. 2019. PMID: 30626685 Free PMC article.
-
CD8+ T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome.J Virol. 2016 Dec 16;91(1):e01825-16. doi: 10.1128/JVI.01825-16. Print 2017 Jan 1. J Virol. 2016. PMID: 27795435 Free PMC article.
-
Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease.J Virol. 2015 Apr;89(7):3659-70. doi: 10.1128/JVI.03427-14. Epub 2015 Jan 14. J Virol. 2015. PMID: 25589660 Free PMC article.
-
Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis.Virol J. 2015 Dec 22;12:218. doi: 10.1186/s12985-015-0446-6. Virol J. 2015. PMID: 26690369 Free PMC article. Review.
-
Animal models of Middle East respiratory syndrome coronavirus infection.Antiviral Res. 2015 Oct;122:28-38. doi: 10.1016/j.antiviral.2015.07.005. Epub 2015 Jul 17. Antiviral Res. 2015. PMID: 26192750 Free PMC article. Review.
Cited by 62 articles
-
A high throughput screen for TMPRSS2 expression identifies FDA-approved and clinically advanced compounds that can limit SARS-CoV-2 entry.Res Sq. 2020 Aug 14:rs.3.rs-48659. doi: 10.21203/rs.3.rs-48659/v1. Preprint. Res Sq. 2020. PMID: 32818215 Free PMC article.
-
Proton Pump Inhibitors are Risk Factors for Viral Infections: Even for COVID-19?Clin Drug Investig. 2020 Aug 10:1-3. doi: 10.1007/s40261-020-00963-x. Online ahead of print. Clin Drug Investig. 2020. PMID: 32779119 Free PMC article. Review.
-
SARS-CoV-2 in wastewater: State of the knowledge and research needs.Sci Total Environ. 2020 Oct 15;739:139076. doi: 10.1016/j.scitotenv.2020.139076. Epub 2020 Apr 30. Sci Total Environ. 2020. PMID: 32758929 Free PMC article. Review.
-
Psychiatric face of COVID-19.Transl Psychiatry. 2020 Jul 30;10(1):261. doi: 10.1038/s41398-020-00949-5. Transl Psychiatry. 2020. PMID: 32732883 Free PMC article. Review.
-
Coronaviruses in wastewater processes: Source, fate and potential risks.Environ Int. 2020 Jul 9;143:105962. doi: 10.1016/j.envint.2020.105962. Online ahead of print. Environ Int. 2020. PMID: 32711332 Free PMC article. Review.
References
-
- Zaki A. M., van Boheemen S., Bestebroer T. M., Osterhaus A. D. M. E., Fouchier R. A. M., Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814–1820 (2012). - PubMed
-
- World Health Organization, MERS-CoV Outbreak Update (World Health Organization, 2017); www.who.int/emergencies/mers-cov/en/.
-
- Assiri A., Al-Tawfiq J. A., Al-Rabeeah A. A., Al-Rabiah F. A., Al-Hajjar S., Al-Barrak A., Flemban H., Al-Nassir W. N., Balkhy H. H., Al-Hakeem R. F., Makhdoom H. Q., Zumla A. I., Memish Z. A., Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet Infect. Dis. 13, 752–761 (2013). - PMC - PubMed
-
- Cauchemez S., Nouvellet P., Cori A., Jombart T., Garske T., Clapham H., Moore S., Mills H. L., Salje H., Collins C., Rodriquez-Barraquer I., Riley S., Truelove S., Algarni H., Alhakeem R., AlHarbi K., Turkistani A., Aguas R. J., Cummings D. A. T., Van Kerkhove M. D., Donnelly C. A., Lessler J., Fraser C., Al-Barrak A., Ferguson N. M., Unraveling the drivers of MERS-CoV transmission. Proc. Natl. Acad. Sci. U.S.A. 113, 9081–9086 (2016). - PMC - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Medical
-
Molecular Biology Databases
-
Miscellaneous