title: Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways.
abstract: 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.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Hin
authors.initials: H
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Microbiology.
authors.forename: Bosco Ho-Yin
authors.initials: BH
authors.lastname: Wong
authors.affiliation: Department of Microbiology.
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Jasper Fuk-Woo
authors.initials: JF
authors.lastname: Chan
authors.affiliation: Department of Microbiology.
authors.forename: Zhong-Shan
authors.initials: ZS
authors.lastname: Cheng
authors.affiliation: Department of Microbiology.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Microbiology.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Microbiology.
authors.forename: Andrew Chak-Yiu
authors.initials: AC
authors.lastname: Lee
authors.affiliation: Department of Microbiology.
authors.forename: Chuangen
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Man-Lung
authors.initials: ML
authors.lastname: Yeung
authors.affiliation: Department of Microbiology.
authors.forename: Jian-Piao
authors.initials: JP
authors.lastname: Cai
authors.affiliation: Department of Surgery, University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Ivy Hau-Yee
authors.initials: IH
authors.lastname: Chan
authors.affiliation: Department of Surgery, University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Wai-Kuen
authors.initials: WK
authors.lastname: Ho
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Kelvin Kai-Wang
authors.initials: KK
authors.lastname: To
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection.
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Research Centre of Infection and Immunology Carol Yu Centre for Infection Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, China.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral; D017209:Apoptosis / Q000502:physiology*; D002144:Callithrix; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*
chemical_list: D000914:Antibodies, Viral; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: MERS-CoV; T lymphocytes; apoptosis; caspase; marmosets; spleen; tonsil