Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways

被引:337
作者
Chu, Hin [1 ,2 ,3 ,4 ]
Zhou, Jie [1 ,2 ,3 ,4 ]
Wong, Bosco Ho-Yin [2 ]
Li, Cun [2 ]
Chan, Jasper Fuk-Woo [1 ,2 ,3 ,4 ]
Cheng, Zhong-Shan [2 ]
Yang, Dong [2 ]
Wang, Dong [2 ]
Lee, Andrew Chak-Yiu [2 ]
Li, Chuangen [2 ]
Yeung, Man-Lung [1 ,2 ,3 ,4 ]
Cai, Jian-Piao [2 ]
Chan, Ivy Hau-Yee [5 ]
Ho, Wai-Kuen [5 ]
To, Kelvin Kai-Wang [1 ,2 ,3 ,4 ]
Zheng, Bo-Jian [1 ,2 ,3 ,4 ]
Yao, Yanfeng [6 ]
Qin, Chuan [6 ]
Yuen, Kwok-Yung [1 ,2 ,3 ,4 ,7 ]
机构
[1] Univ Hong Kong, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China
[3] Univ Hong Kong, Res Ctr Infect & Immunol, Pokfulam, Hong Kong, Peoples R China
[4] Univ Hong Kong, Carol Yu Ctr Infect, Pokfulam, Hong Kong, Peoples R China
[5] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China
[6] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China
[7] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou, Zhejiang, Peoples R China
关键词
MERS-CoV; T lymphocytes; apoptosis; caspase; tonsil; spleen; marmosets; INNATE ANTIVIRAL RESPONSE; DIPEPTIDYL PEPTIDASE-IV; PROGRAMMED CELL-DEATH; MERS-COV; INTERFERON ANTAGONIST; SARS CORONAVIRUS; RHESUS MACAQUES; SAUDI-ARABIA; REPLICATION; DISEASE;
D O I
10.1093/infdis/jiv380
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.
引用
收藏
页码:904 / 914
页数:11
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