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C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting-1 PRF and the NS3 Protein

查看全文 作　　者：Du [1]Yu;Yundi [1]Zhao;Junhui [1]Pan;Xingmiao [1]Yang;Zhenjie [1]Liang;Shengda [1]Xie;Ruibing [1]Cao 高影响力作者 机构地区：[1]MOE Joint International Research Laboratory of Animal Health and Food Safety,College of Veterinary Medicine,Nanjing Agricultural University,Nanjing 210095,China高影响力机构 出　　处：《Virologica Sinica》索引2021年第36卷第6期,共13页高影响力期刊 基　　金：This work was supported by grants from the National Natural Science Foundation of China(Grant No.31772756);the National Key Research and Development Program of China(Grant No.2016YFD0500402);the Priority Academic Program Development of Jiangsu Higher Education Institutions。 摘　　要：The Japanese encephalitis serogroup of the neurogenic Flavivirus has a specific feature that expresses a non-structural protein NS1'produced through a programmed-1 ribosomal frameshifting(-1 PRF).Herein,C19orf66,a novel member of interferon-stimulated gene(ISG)products,exhibited significant activity of antagonizing Japanese encephalitis virus(JEV)infection.Overexpression of C19orf66 in 293T cells significantly inhibited JEV replication,while knock-down of endogenous C19orf66 in HeLa cells and A549 cells significantly increased virus replication.Notably,C19orf66 had an inhibitory effect on frameshift production of JEV NS1'.The inhibition was more significant when C19orf66 and JEV NS1-NS2A were co-expressed in the 293T cells.Both C19orf66-209 and C19orf66-Zinc^(mut) did not significantly change the NS1'to NS1 ratio and had weaker antiviral effects than C19orf66.Similarly,C19orf66-209 and C19orf66-Zinc^(mut) had no significant effect on the expression of the JEV NS3 protein,whose expression was down-regulated by C19orf66 via the lysosome-dependent pathway.These findings suggest that C19orf66 may possess at least two different mechanisms of antagonizing JEV infection.This study identified C19orf66 as a novel interferon-stimulated gene product that can inhibit JEV replication by targeting-1 PRF and the NS3 protein.The study provides baseline information for the future development of broad-spectrum antiviral agents against JEV. 关 键 词：Japanese encephalitis virus(JEV) C19orf66 Programmed-1 ribosomal frameshifting(-1 PRF) NS1’ NS3
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