國家衛生研究院 NHRI:Item 3990099045/12151

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12151

Title:	A dengue virus type 2 (DENV-2) NS4B-interacting host factor, SERP1, reduces DENV-2 production by suppressing viral RNA replication
Authors:	Tian, JN;Yang, CC;Chuang, CK;Tsai, MH;Wu, RH;Chen, CT;Yueh, A
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Host cells infected with dengue virus (DENV) often trigger endoplasmic reticulum (ER) stress, a key process that allows viral reproduction, without killing the host cells until the late stage of the virus life-cycle. However, little is known regarding which DENV viral proteins interact with the ER machinery to support viral replication. In this study, we identified and characterized a novel host factor, stress-associated ER protein 1 (SERP1), which interacts with the DENV type 2 (DENV-2) NS4B protein by several assays, for example, yeast two-hybrid, subcellular localization, NanoBiT complementation, and co-immunoprecipitation. A drastic increase (34.5-fold) in the SERP1 gene expression was observed in the DENV-2-infected or replicon-transfected Huh7.5 cells. The SERP1 overexpression inhibited viral yields (37-fold) in the DENV-2-infected Huh7.5 cells. In contrast, shRNAi-knockdown and the knockout of SERP1 increased the viral yields (3.4- and 16-fold, respectively) in DENV-2-infected HEK-293 and Huh7.5 cells, respectively. DENV-2 viral RNA replication was severely reduced in stable SERP1-expressing Huh7.5 cells transfected with DENV-2 replicon plasmids. The overexpression of DENV-2 NS4B alleviated the inhibitory effect of SERP1 on DENV-2 RNA replication. Taking these results together, we hypothesized that SERP1 may serve as an antiviral player during ER stress to restrict DENV-2 infection. Our studies revealed novel anti-DENV drug targets that may facilitate anti-DENV drug discovery.
Date:	2019-08-27
Relation:	Viruses. 2019 Aug 27;11(9):Article number 787.
Link to:	http://dx.doi.org/10.3390/v11090787
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1999-4915&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000487962400051
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85071616169
Appears in Collections:	[Yueh Andrew Yueh] Periodical Articles [Chiung-Tong Chen] Periodical Articles

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