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
相关论文
共 50 条
[1]   Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels [J].
Adney, Danielle R. ;
van Doremalen, Neeltje ;
Brown, Vienna R. ;
Bushmaker, Trenton ;
Scott, Dana ;
de Wit, Emmie ;
Bowen, Richard A. ;
Munster, Vincent J. .
EMERGING INFECTIOUS DISEASES, 2014, 20 (12) :1999-2005
[2]   Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description [J].
Al-Abdallat, Mohammad Mousa ;
Payne, Daniel C. ;
Alqasrawi, Sultan ;
Rha, Brian ;
Tohme, Rania A. ;
Abedi, Glen R. ;
Al Nsour, Mohannad ;
Iblan, Ibrahim ;
Jarour, Najwa ;
Farag, Noha H. ;
Haddadin, Aktham ;
Al-Sanouri, Tarek ;
Tamin, Azaibi ;
Harcourt, Jennifer L. ;
Kuhar, David T. ;
Swerdlow, David L. ;
Erdman, Dean D. ;
Pallansch, Mark A. ;
Haynes, Lia M. ;
Gerber, Susan I. .
CLINICAL INFECTIOUS DISEASES, 2014, 59 (09) :1225-1233
[3]   Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study [J].
Assiri, Abdullah ;
Al-Tawfiq, Jaffar A. ;
Al-Rabeeah, Abdullah A. ;
Al-Rabiah, Fahad A. ;
Al-Hajjar, Sami ;
Al-Barrak, Ali ;
Flemban, Hesham ;
Al-Nassir, Wafa N. ;
Balkhy, Hanan H. ;
Al-Hakeem, Rafat F. ;
Makhdoom, Hatem Q. ;
Zumla, Alimuddin I. ;
Memish, Ziad A. .
LANCET INFECTIOUS DISEASES, 2013, 13 (09) :752-761
[4]  
Bermingham A, 2012, EUROSURVEILLANCE, V17, P6
[5]   Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease [J].
Chan, Jasper F. W. ;
Lau, Susanna K. P. ;
To, Kelvin K. W. ;
Cheng, Vincent C. C. ;
Woo, Patrick C. Y. ;
Yuen, Kwok-Yung .
CLINICAL MICROBIOLOGY REVIEWS, 2015, 28 (02) :465-522
[6]   Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus [J].
Chan, Jasper F. W. ;
Chan, Kwok-Hung ;
Kao, Richard Y. T. ;
To, Kelvin K. W. ;
Zheng, Bo-Jian ;
Li, Clara P. Y. ;
Li, Patrick T. W. ;
Dai, Jun ;
Mok, Florence K. Y. ;
Chen, Honglin ;
Hayden, Frederick G. ;
Yuen, Kwok-Yung .
JOURNAL OF INFECTION, 2013, 67 (06) :606-616
[7]   Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? [J].
Chan, Jasper F. W. ;
Li, Kenneth S. M. ;
To, Kelvin K. W. ;
Cheng, Vincent C. C. ;
Chen, Honglin ;
Yuen, Kwok-Yung .
JOURNAL OF INFECTION, 2012, 65 (06) :477-489
[8]   Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset [J].
Chan, Jasper Fuk-Woo ;
Yao, Yanfeng ;
Yeung, Man-Lung ;
Deng, Wei ;
Bao, Linlin ;
Jia, Lilong ;
Li, Fengdi ;
Xiao, Chong ;
Gao, Hong ;
Yu, Pin ;
Cai, Jian-Piao ;
Chu, Hin ;
Zhou, Jie ;
Chen, Honglin ;
Qin, Chuan ;
Yuen, Kwok-Yung .
JOURNAL OF INFECTIOUS DISEASES, 2015, 212 (12) :1904-1913
[9]   Development and Evaluation of Novel Real-Time Reverse Transcription-PCR Assays with Locked Nucleic Acid Probes Targeting Leader Sequences of Human-Pathogenic Coronaviruses [J].
Chan, Jasper Fuk-Woo ;
Choi, Garnet Kwan-Yue ;
Tsang, Alan Ka-Lun ;
Tee, Kah-Meng ;
Lam, Ho-Yin ;
Yip, Cyril Chik-Yan ;
To, Kelvin Kai-Wang ;
Cheng, Vincent Chi-Chung ;
Yeung, Man-Lung ;
Lau, Susanna Kar-Pui ;
Woo, Patrick Chiu-Yat ;
Chan, Kwok-Hung ;
Tang, Bone Siu-Fai ;
Yuen, Kwok-Yung .
JOURNAL OF CLINICAL MICROBIOLOGY, 2015, 53 (08) :2722-2726
[10]   Interspecies transmission and emergence of novel viruses: lessons from bats and birds [J].
Chan, Jasper Fuk-Woo ;
To, Kelvin Kai-Wang ;
Tse, Herman ;
Jin, Dong-Yan ;
Yuen, Kwok-Yung .
TRENDS IN MICROBIOLOGY, 2013, 21 (10) :544-555