HTNV Sensitizes Host Toward TRAIL-Mediated Apoptosis—A Pivotal Anti-hantaviral Role of TRAIL

Frontiers in Immunology

Chao-Jie Zhong¹  Shuang Lu¹  Yong-Zhen Zhang¹  Xin Wang¹  Ning Li¹  Mei-Rong Wang²  Fan Luo³  Wei Hou³  Yu-xing Zan³  Hai-Tao Hu³  Qing-Zhou Chen³  Ni Zhu³  Hai-Rong Xiong³ 

[1] Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, China;Department of Microbiology, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, China;;State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy &

关键词: HFRS;    HTNV;    TRAIL;    apoptosis;    IFN-β;   

DOI  :  10.3389/fimmu.2020.01072

来源: DOAJ

【 摘 要 】

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-β production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-β production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-β production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.

【 授权许可】

Unknown