Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential.
Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential.
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DOI：
10.1073/pnas.2103984118
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发表时间：
2021-06-22
影响因子：
11.1
通讯作者：
Peiris M
中科院分区：
文献类型：
--
作者：
Zhou Z;Hui KPY;So RTY;Lv H;Perera RAPM;Chu DKW;Gelaye E;Oyas H;Njagi O;Abayneh T;Kuria W;Walelign E;Wanglia R;El Masry I;Von Dobschuetz S;Kalpravidh W;Chevalier V;Miguel E;Fassi-Fihri O;Trarore A;Liang W;Wang Y;Nicholls JM;Zhao J;Chan MCW;Poon LLM;Mok CKP;Peiris M
尽管非洲有大量感染MERS-CoV的单峰骆驼，但却没有人畜共患MERS-CoV，这仍然是一个谜。我们证明了来自非洲的地理和遗传上不同的病毒在人肺中的复制能力较低，这为非洲没有严重的MERS疾病提供了一个可能的解释。研究结果表明，中东呼吸综合征冠状病毒目前在阿拉伯半岛根深蒂固，对人类的致病潜力增加。我们证明，穗蛋白有助于这种表型差异。如果来自阿拉伯半岛的致病性进化枝B病毒被引入非洲，它们很可能像在阿拉伯半岛那样成为优势病毒，并与非洲的不利健康影响和增加的大流行威胁相关。冠状病毒是具有大流行潜力的病原体。中东呼吸综合征冠状病毒（MERS-CoV）引起全球公共卫生关注的人畜共患呼吸道疾病，单峰骆驼是唯一被证实的人畜共患感染源。超过70%的MERS-CoV感染单峰骆驼发现于东非、北非和西非，但人畜共患MERS疾病仅在阿拉伯半岛报告。我们比较了来自阿拉伯半岛的进化枝A和B病毒与在东非（埃及、肯尼亚和埃塞俄比亚）、北非（摩洛哥）和西非（尼日利亚和布基纳法索）发现的遗传多样性进化枝C病毒的病毒复制能力。来自非洲的病毒在人肺的离体培养物和实验感染的人-DPP 4（hDPP 4）敲入小鼠的肺中具有较低的复制能力。我们使用表达来自沙特阿拉伯进化枝A原型株（EMC）或非洲进化枝C1.1病毒的MERS-CoV刺突的慢病毒假型，并证明进化枝C1.1刺突与病毒进入呼吸道上皮细胞系Calu-3的减少有关。通过反向遗传学产生的具有来自EMC或进化枝C1.1的刺突蛋白的同基因EMC病毒表明，进化枝C1.1刺突与体外Calu-3细胞、离体人支气管和体内hDPP 4敲入小鼠肺中的病毒复制能力降低相关。这些发现可能解释了为什么迄今为止非洲尚未报告人畜共患MERS疾病，尽管暴露于MERS-CoV并感染。
The absence of zoonotic MERS-CoV in Africa in spite of an abundance of MERS-CoV–infected dromedaries has remained an enigma. We demonstrate that geographically and genetically distinct viruses from Africa have low replication competence in the human lung, providing a possible explanation for the absence of severe MERS disease in Africa. The findings suggest that MERS-CoV now entrenched in the Arabian Peninsula has acquired increased pathogenic potential for humans. We demonstrate that the spike protein contributes to this phenotypic difference. If pathogenic clade B viruses from the Arabian Peninsula are introduced into Africa, they are likely to become dominant, as they have in the Arabian Peninsula, and to be associated with adverse health impacts in Africa and increased pandemic threat. Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV–infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.
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影响因子：
19
作者：
Abbad, Anass;Perera, Ranawaka A. P. M.;Nourlil, Jalal
通讯作者：
Nourlil, Jalal
影响因子：
4.3
作者：
Korea Centers for Disease Control and Prevention
通讯作者：
Korea Centers for Disease Control and Prevention
影响因子：
13.2
作者：
Millet, Jean Kaoru;Goldstein, Monty E.;Labitt, Rachael N.;Hsu, Hung-Lun;Daniel, Susan;Whittaker, Gary R.
通讯作者：
Whittaker, Gary R.
沙特阿拉伯骆驼工人中中东呼吸综合征冠状病毒感染率很高
影响因子：
6.4
作者：
Alshukairi AN;Zheng J;Zhao J;Nehdi A;Baharoon SA;Layqah L;Bokhari A;Al Johani SM;Samman N;Boudjelal M;Ten Eyck P;Al-Mozaini MA;Zhao J;Perlman S;Alagaili AN
通讯作者：
Alagaili AN
影响因子：
11.8
作者：
Liljander, Anne;Meyer, Benjamin;Corman, Victor Max
通讯作者：
Corman, Victor Max