RT Journal Article
SR Electronic
T1 Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaao4966
DO 10.1126/sciadv.aao4966
VO 3
IS 11
A1 Zhou, Jie
A1 Li, Cun
A1 Zhao, Guangyu
A1 Chu, Hin
A1 Wang, Dong
A1 Yan, Helen Hoi-Ning
A1 Poon, Vincent Kwok-Man
A1 Wen, Lei
A1 Wong, Bosco Ho-Yin
A1 Zhao, Xiaoyu
A1 Chiu, Man Chun
A1 Yang, Dong
A1 Wang, Yixin
A1 Au-Yeung, Rex K. H.
A1 Chan, Ivy Hau-Yee
A1 Sun, Shihui
A1 Chan, Jasper Fuk-Woo
A1 To, Kelvin Kai-Wang
A1 Memish, Ziad A.
A1 Corman, Victor M.
A1 Drosten, Christian
A1 Hung, Ivan Fan-Ngai
A1 Zhou, Yusen
A1 Leung, Suet Yi
A1 Yuen, Kwok-Yung
YR 2017
UL http://advances.sciencemag.org/content/3/11/eaao4966.abstract
AB 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.