首页|Ebola virus VP35 perturbs type Ⅰ interferon signaling to facilitate viral replication

Ebola virus VP35 perturbs type Ⅰ interferon signaling to facilitate viral replication

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As one of the deadliest viruses,Ebola virus(EBOV)causes lethal hemorrhagic fevers in humans and nonhuman primates.The suppression of innate immunity leads to robust systemic virus replication of EBOV,leading to enhanced transmission.However,the mechanism of EBOV-host interaction is not fully understood.Here,we identified multiple dysregulated genes in early stage of EBOV infection through transcriptomic analysis,which are highly clustered to Jak-STAT signaling.EBOV VP35 and VP30 were found to inhibit type Ⅰ interferon(IFN)signaling.Moreover,exog-enous expression of VP35 blocks the phosphorylation of endogenous STAT1,and suppresses nuclear translocation of STAT1.Using serial truncated mutations of VP35,N-terminal 1-220 amino acid residues of VP35 were identified to be essential for blocking on type Ⅰ IFN signaling.Remarkably,VP35 of EBOV suppresses type Ⅰ IFN signaling more efficiently than those of Bundibugyo virus(BDBV)and Marburg virus(MARV),resulting in stable replication to facilitate the pathogenesis.Altogether,this study enriches understanding on EBOV evasion of innate immune response,and provides insights into the interplay between filoviruses and host.

Ebola virus(EBOV)Type Ⅰ interferon(IFN)signalingViral replication

Zengguo Cao、Chenchen Liu、Cheng Peng、Yong Ran、Yulin Yao、Gengfu Xiao、Entao Li、Zixi Chen、Xia Chuai、Sandra Chiu

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Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China

University of Chinese Academy of Sciences,Beijing,100190,China

National Biosafety Laboratory,Chinese Academy of Sciences,Wuhan,430020,China

Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230026,China

Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science,Shenzhen Engineering Laboratory for Marine Algal Biotechnology,Guangdong Provincial Key Laboratory for Plant Epigenetics,College of Life Sciences and Oceanography,Shenzhen University,Shenzhen 518060,China

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BSL-4 Laboratory,Wuhan Institute of Virology,Chinese Academy of SciencesNational Biosafety Laboratory(Wuhan)Chinese Academy of SciencesCenter for Biosafety Mega-Science,Chinese Academy of SciencesNational Virus Resource CenterStrategic Priority Research Program of the Chinese Academy of SciencesNational Natural Science Foundation of China

XDB049000082202521

2023

10.1016/j.virs.2023.10.004

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(6)
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