Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus.
Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus.
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DOI：
10.1126/sciadv.aao4966
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发表时间：
2017-11
期刊：
影响因子：
13.6
通讯作者：
Yuen KY
中科院分区：
文献类型：
--
作者：
Zhou J;Li C;Zhao G;Chu H;Wang D;Yan HH;Poon VK;Wen L;Wong BH;Zhao X;Chiu MC;Yang D;Wang Y;Au-Yeung RKH;Chan IH;Sun S;Chan JF;To KK;Memish ZA;Corman VM;Drosten C;Hung IF;Zhou Y;Leung SY;Yuen KY
人类肠道是感染MERS冠状病毒的替代途径。自2012年以来，中东呼吸综合征冠状病毒(MERS-CoV)已引起人类呼吸道感染，病死率很高。然而，病毒的传播方式还不是很清楚。流行病学和病毒学研究的结果促使我们假设，人类胃肠道可能是感染MERS冠状病毒的替代途径。我们证明，人的原代肠道上皮细胞、小肠外植体和肠道器官对MERS冠状病毒高度敏感，并能维持病毒的强劲复制。我们还在一名临床患者的粪便标本中发现了肠道MERS-CoV感染的证据。MERS-CoV对进食状态的胃肠液有相当大的抵抗力，但对高度酸性的空腹状态胃液的耐受性较差。在培养于Transwell贴片中的极化Caco-2细胞中，MERS冠状病毒顶端接种比基侧接种更有效地建立感染。值得注意的是，直接胃内接种MERS-CoV会导致人类DPP4转基因小鼠的致死性感染。组织学检查显示所有接种MERS冠状病毒的小鼠都有肠道感染，表现为小肠中病毒阳性细胞的存在，进行性炎症和上皮变性，这些在质子泵抑制剂潘托拉唑处理的小鼠中被夸大了。随着肠道感染的进展，肺组织中出现炎症、病毒阳性细胞和活病毒，提示继发性呼吸道感染的发生。综上所述，这些数据表明，人类肠道可能是MERS冠状病毒的替代感染途径。
Human intestinal tract as an alternative route to acquire MERS-CoV infection. 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.
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DOI：
10.1016/s0140-6736(03)13077-2
发表时间：
2003-04-19
期刊：
Lancet (London, England)
影响因子：
--
作者：
Peiris JS;Lai ST;Poon LL;Guan Y;Yam LY;Lim W;Nicholls J;Yee WK;Yan WW;Cheung MT;Cheng VC;Chan KH;Tsang DN;Yung RW;Ng TK;Yuen KY;SARS study group
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SARS study group
影响因子：
12.8
作者：
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通讯作者：
Choi S
DOI：
10.1073/pnas.1519235113
发表时间：
2016-08-09
影响因子：
11.1
作者：
Cauchemez, Simon;Nouvellet, Pierre;Ferguson, Neil M.
通讯作者：
Ferguson, Neil M.
影响因子：
13.5
作者：
Martin, A;Lemon, SM
通讯作者：
Lemon, SM
影响因子：
11.8
作者：
Corman, Victor M.;Albarrak, Ali M.;Memish, Ziad A.
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Memish, Ziad A.