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

Chu, Hin; Zhou, Jie; Wong, Bosco Ho-Yin; Li, Cun; Chan, Jasper Fuk-Woo; Cheng, Zhong-Shan; Yang, Dong; Wang, Dong; Lee, Andrew Chak-Yiu; Li, Chuangen; Yeung, Man-Lung; Cai, Jian-Piao; Chan, Ivy Hau-Yee; Ho, Wai-Kuen; To, Kelvin Kai-Wang; Zheng, Bo-Jian; Yao, Yanfeng; Qin, Chuan; Yuen, Kwok-Yung

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.