Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

被引:245
作者
de Wit, Emmie [1 ]
Rasmussen, Angela L. [4 ]
Falzarano, Darryl [1 ]
Bushmaker, Trenton [1 ]
Feldmann, Friederike [2 ]
Brining, Douglas L. [2 ]
Fischer, Elizabeth R. [3 ]
Martellaro, Cynthia [1 ]
Okumura, Atsushi [4 ]
Chang, Jean [4 ]
Scott, Dana [2 ]
Benecke, Arndt G. [4 ,5 ]
Katze, Michael G. [4 ]
Feldmann, Heinz [1 ,6 ]
Munster, Vincent J. [1 ]
机构
[1] NIAID, Lab Virol, NIH, Hamilton, MT 59840 USA
[2] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA
[3] NIAID, Microscopy Unit, Res Technol Branch, Div Intramural Res,NIH, Hamilton, MT 59840 USA
[4] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[5] Univ Paris 06, Dept Biol, Ctr Natl Rech Sci, Unite Mixte Rech 7224, F-75005 Paris, France
[6] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada
基金
美国国家卫生研究院;
关键词
emerging infectious disease; DPP4; CLINICAL-FEATURES; AFRICAN-GREEN; ANIMAL-MODEL; VIRUS; PNEUMONIA; SYSTEM; BATS;
D O I
10.1073/pnas.1310744110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 x 10(6) 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.
引用
收藏
页码:16598 / 16603
页数:6
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