Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A.
Hepatitis C virus (HCV) uses components of the very-low-density lipoprotein (VLDL) pathway for assembly/release. We previously reported that hepatocyte nuclear factor 4α (HNF4α) participates in HCV assembly/release through downstream factors those participate in VLDL assembly/secretion. Cell-death-inducing DFFA-like effector B (CIDEB) is an important regulator of the VLDL pathway. CIDEB is required for entry of HCV particles from cell culture (HCVcc), but the effects of CIDEB on the post-entry steps of the HCV lifecycle are unclear. In the present study, we determined that CIDEB is required for HCV assembly in addition to HCVcc entry. Furthermore, CIDEB interacts with the HCV NS5A protein, and the N terminus of CIDEB and the domain I of NS5A are involved in this interaction. Moreover, CIDEB silencing impairs the association of apolipoprotein E (ApoE) with HCV particles. Interestingly, CIDEB is also required for the post-entry stages of the dengue virus (DENV) life cycle. Collectively, these results indicate that CIDEB is a new host factor that is involved in HCV assembly, presumably by interacting with viral protein, providing new insight into the exploitation of the VLDL regulator CIDEB by HCV.
State Key Laboratory of Respiratory Disease, Guangzhou Hoffmann Institute, College of Basic Sciences, Guangzhou Medical University, Guangzhou, China.|Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Hua
H
Cai
State Key Laboratory of Respiratory Disease, Guangzhou Hoffmann Institute, College of Basic Sciences, Guangzhou Medical University, Guangzhou, China.|Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Wenxia
W
Yao
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|The Brown Foundation Institute of Molecular Medicine at the University of Texas Health Science Center at Houston, Houston, TX, USA.
Leike
L
Li
State Key Laboratory of Respiratory Disease, Guangzhou Hoffmann Institute, College of Basic Sciences, Guangzhou Medical University, Guangzhou, China.
Xinlei
X
Li
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Longbo
L
Hu
State Key Laboratory of Respiratory Disease, Guangzhou Hoffmann Institute, College of Basic Sciences, Guangzhou Medical University, Guangzhou, China.
Runming
R
Mai
State Key Laboratory of Respiratory Disease, Guangzhou Hoffmann Institute, College of Basic Sciences, Guangzhou Medical University, Guangzhou, China.|Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Tao
T
Peng
D001057:Apolipoproteins E / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D016923:Cell Death; D020868:Gene Silencing; D057809:HEK293 Cells; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D053586:Virus Internalization; D012324:RNA-Dependent RNA Polymerase
D001057:Apolipoproteins E; D051017:Apoptosis Regulatory Proteins; D017361:Viral Nonstructural Proteins; C112511:CIDEB protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase