ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the <i>Flavivirus genus</i>, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a se...

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Main Authors: Dingwen Hu, Haimei Zou, Weijie Chen, Yuting Li, Ziqing Luo, Xianyang Wang, Dekuan Guo, Yu Meng, Feng Liao, Wenbiao Wang, Ying Zhu, Jianguo Wu, Geng Li
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/1/144
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author Dingwen Hu
Haimei Zou
Weijie Chen
Yuting Li
Ziqing Luo
Xianyang Wang
Dekuan Guo
Yu Meng
Feng Liao
Wenbiao Wang
Ying Zhu
Jianguo Wu
Geng Li
author_facet Dingwen Hu
Haimei Zou
Weijie Chen
Yuting Li
Ziqing Luo
Xianyang Wang
Dekuan Guo
Yu Meng
Feng Liao
Wenbiao Wang
Ying Zhu
Jianguo Wu
Geng Li
author_sort Dingwen Hu
collection DOAJ
description Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the <i>Flavivirus genus</i>, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.
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spelling doaj.art-f6f96fed87e0466298b3e3a0e423ab3d2023-12-01T01:11:10ZengMDPI AGViruses1999-49152023-01-0115114410.3390/v15010144ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope ProteinDingwen Hu0Haimei Zou1Weijie Chen2Yuting Li3Ziqing Luo4Xianyang Wang5Dekuan Guo6Yu Meng7Feng Liao8Wenbiao Wang9Ying Zhu10Jianguo Wu11Geng Li12State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaThe Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLaboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaMedical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, ChinaZika virus (ZIKV) is an RNA-enveloped virus that belongs to the <i>Flavivirus genus</i>, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.https://www.mdpi.com/1999-4915/15/1/144Zika viruspalmitoylation2-BPenvelope proteinZDHHC11
spellingShingle Dingwen Hu
Haimei Zou
Weijie Chen
Yuting Li
Ziqing Luo
Xianyang Wang
Dekuan Guo
Yu Meng
Feng Liao
Wenbiao Wang
Ying Zhu
Jianguo Wu
Geng Li
ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
Viruses
Zika virus
palmitoylation
2-BP
envelope protein
ZDHHC11
title ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
title_full ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
title_fullStr ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
title_full_unstemmed ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
title_short ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein
title_sort zdhhc11 suppresses zika virus infections by palmitoylating the envelope protein
topic Zika virus
palmitoylation
2-BP
envelope protein
ZDHHC11
url https://www.mdpi.com/1999-4915/15/1/144
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