Back to Search
Start Over
Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
- Source :
- Science Advances
- Publication Year :
- 2017
- Publisher :
- American Association for the Advancement of Science (AAAS), 2017.
-
Abstract
- Human intestinal tract as an alternative route to acquire MERS-CoV infection.<br />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.
- Subjects :
- 0301 basic medicine
Middle East respiratory syndrome coronavirus
Dipeptidyl Peptidase 4
viruses
Mice, Transgenic
Inflammation
Biology
medicine.disease_cause
Feces
Mice
03 medical and health sciences
0302 clinical medicine
Virology
Intestine, Small
medicine
Animals
Humans
Health and Medicine
030212 general & internal medicine
Respiratory system
Lung
Pantoprazole
Research Articles
Multidisciplinary
Human gastrointestinal tract
virus diseases
SciAdv r-articles
Respiratory infection
Epithelial Cells
respiratory system
biochemical phenomena, metabolism, and nutrition
Small intestine
respiratory tract diseases
3. Good health
030104 developmental biology
medicine.anatomical_structure
Viral replication
Immunology
Middle East Respiratory Syndrome Coronavirus
RNA, Viral
Female
Caco-2 Cells
medicine.symptom
Coronavirus Infections
Research Article
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 3
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi.dedup.....6c0d89ff3ef44127f2aecf464252f2b1
- Full Text :
- https://doi.org/10.1126/sciadv.aao4966