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

(Source: Science Advance, March 25, 2020)


Before Covid 19, since 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused high case fatality rate. But, the method of virus spread is not well understood. The findings of epi-demiological and virological studies prompted us to theorize 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 vulnerable to MERS-CoV and can sustain strong viral reproduction. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to absorptive-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

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