Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells

IntroductionThe Zika virus (ZIKV) envelope (E) protein is critical for viral replication and host interactions. Although glycosylation of the E protein is known to influence viral infectivity and immune evasion, the specific functional roles of E protein glycosylation in ZIKV infectivity in mosquito...

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Main Authors: Wen-Jing Wang, Zi-Han Wang, Jing Li, Sai-Ya Ma, Mei He, Meng-Xuan Liu, Yu-Fei Zhan, Feng Jin, Guosheng Qu, Chunhong Yin, Jie Tong
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1603083/full
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author Wen-Jing Wang
Wen-Jing Wang
Zi-Han Wang
Zi-Han Wang
Jing Li
Jing Li
Sai-Ya Ma
Sai-Ya Ma
Mei He
Mei He
Meng-Xuan Liu
Meng-Xuan Liu
Yu-Fei Zhan
Yu-Fei Zhan
Feng Jin
Feng Jin
Guosheng Qu
Guosheng Qu
Chunhong Yin
Chunhong Yin
Jie Tong
Jie Tong
author_facet Wen-Jing Wang
Wen-Jing Wang
Zi-Han Wang
Zi-Han Wang
Jing Li
Jing Li
Sai-Ya Ma
Sai-Ya Ma
Mei He
Mei He
Meng-Xuan Liu
Meng-Xuan Liu
Yu-Fei Zhan
Yu-Fei Zhan
Feng Jin
Feng Jin
Guosheng Qu
Guosheng Qu
Chunhong Yin
Chunhong Yin
Jie Tong
Jie Tong
author_sort Wen-Jing Wang
collection DOAJ
description IntroductionThe Zika virus (ZIKV) envelope (E) protein is critical for viral replication and host interactions. Although glycosylation of the E protein is known to influence viral infectivity and immune evasion, the specific functional roles of E protein glycosylation in ZIKV infectivity in mosquito cells remain unclear.MethodsIn this study, we generated a deglycosylation mutant ZIKV with a T156I substitution in the E protein and investigated its effects on viral replication and viral-host interactions in mosquito C6/36 cells.ResultsOur results demonstrated that the T156I mutant exhibited attenuated replication compared to the wild-type virus during the early stages (0-24 hours) post-virus infection in mosquito C6/36 cells. This attenuation was associated with reduced E protein expression, which was regulated at the post-transcriptional level. RNA sequencing further revealed that the T156I mutation significantly altered virus-host interactions, particularly affecting the extracellular matrix (ECM) signaling pathway. Notably, several genes involved in the ECM signaling pathway, including THBS1, ITGAL, IL-1A, and CXCL8, were found to inhibit the T156I mutant but not the wild-type ZIKV. Structural analysis and in silico molecular docking suggested that the T156I mutation impaired the stability of the E protein dimer rather than its interactions with neutralizing antibodies.DiscussionCollectively, these findings provide novel insights into the role of E protein glycosylation in ZIKV infection, and may have significant implications for anti-ZIKV strategies.
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spelling doaj-art-2fb4f10e37bf4142afab9a86ae7bda312025-08-25T05:25:30ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16030831603083Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cellsWen-Jing Wang0Wen-Jing Wang1Zi-Han Wang2Zi-Han Wang3Jing Li4Jing Li5Sai-Ya Ma6Sai-Ya Ma7Mei He8Mei He9Meng-Xuan Liu10Meng-Xuan Liu11Yu-Fei Zhan12Yu-Fei Zhan13Feng Jin14Feng Jin15Guosheng Qu16Guosheng Qu17Chunhong Yin18Chunhong Yin19Jie Tong20Jie Tong21College of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaShandong Center for Disease Control and Prevention, Infectious Disease Control Institute, Shandong, ChinaShandong Provincial Key Laboratory of Intelligent Monitoring, Early Warning, Prevention and Control for Infectious Diseases, Shandong, ChinaCollege of Life Sciences, Hebei University, Baoding, ChinaSchool of Life Sciences and Green Development, Hebei University, Baoding, ChinaIntroductionThe Zika virus (ZIKV) envelope (E) protein is critical for viral replication and host interactions. Although glycosylation of the E protein is known to influence viral infectivity and immune evasion, the specific functional roles of E protein glycosylation in ZIKV infectivity in mosquito cells remain unclear.MethodsIn this study, we generated a deglycosylation mutant ZIKV with a T156I substitution in the E protein and investigated its effects on viral replication and viral-host interactions in mosquito C6/36 cells.ResultsOur results demonstrated that the T156I mutant exhibited attenuated replication compared to the wild-type virus during the early stages (0-24 hours) post-virus infection in mosquito C6/36 cells. This attenuation was associated with reduced E protein expression, which was regulated at the post-transcriptional level. RNA sequencing further revealed that the T156I mutation significantly altered virus-host interactions, particularly affecting the extracellular matrix (ECM) signaling pathway. Notably, several genes involved in the ECM signaling pathway, including THBS1, ITGAL, IL-1A, and CXCL8, were found to inhibit the T156I mutant but not the wild-type ZIKV. Structural analysis and in silico molecular docking suggested that the T156I mutation impaired the stability of the E protein dimer rather than its interactions with neutralizing antibodies.DiscussionCollectively, these findings provide novel insights into the role of E protein glycosylation in ZIKV infection, and may have significant implications for anti-ZIKV strategies.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1603083/fullZika virusE glycoproteinmosquito cellsECM signaling pathwayE-dimer
spellingShingle Wen-Jing Wang
Wen-Jing Wang
Zi-Han Wang
Zi-Han Wang
Jing Li
Jing Li
Sai-Ya Ma
Sai-Ya Ma
Mei He
Mei He
Meng-Xuan Liu
Meng-Xuan Liu
Yu-Fei Zhan
Yu-Fei Zhan
Feng Jin
Feng Jin
Guosheng Qu
Guosheng Qu
Chunhong Yin
Chunhong Yin
Jie Tong
Jie Tong
Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
Frontiers in Microbiology
Zika virus
E glycoprotein
mosquito cells
ECM signaling pathway
E-dimer
title Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
title_full Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
title_fullStr Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
title_full_unstemmed Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
title_short Deficient of glycosylation site in the envelop protein attenuated Zika virus replication in mosquito cells
title_sort deficient of glycosylation site in the envelop protein attenuated zika virus replication in mosquito cells
topic Zika virus
E glycoprotein
mosquito cells
ECM signaling pathway
E-dimer
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1603083/full
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