Apolipoprotein E but not B is Required for the Formation of Infectious Hepatitis C Virus Particles

Authors

Jieyun Jiang, University of KentuckyFollow
Guangxiang Luo, University of Kentucky

Abstract

Our previous studies have found that hepatitis C virus (HCV) particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. Studies by others, however, suggested that both microsomal transfer protein (MTP) and apoB are important for HCV production. To define the roles of apoB and apoE in the HCV life cycle, we developed a single-cycle HCV growth assay to determine the correlation of HCV assembly with apoB and apoE expression, as well as the influence of MTP inhibitors on the formation of HCV particles. The small interfering RNA (siRNA)-mediated knockdown of apoE expression remarkably suppressed the formation of HCV particles. However, apoE expressed ectopically could restore the defect of HCV production posed by the siRNA-mediated knockdown of endogenous apoE expression. In contrast, apoB-specific antibodies and siRNAs had no significant effect on HCV infectivity and production, respectively, suggesting that apoB does not play a significant role in the HCV life cycle. Additionally, two MTP inhibitors, CP-346086 and BMS-2101038, efficiently blocked secretion of apoB-containing lipoproteins but did not affect HCV production unless apoE expression and secretion were inhibited. At higher concentrations, however, MTP inhibitors blocked apoE expression and secretion and consequently suppressed the formation of HCV particles. Furthermore, apoE was found to be sensitive to trypsin digestion and to interact with NS5A in purified HCV particles and HCV-infected cells, as demonstrated by coimmunoprecipitation. Collectively, these findings demonstrate that apoE but not apoB is required for HCV assembly, probably via a specific interaction with NS5A.

Document Type

Article

Publication Date

12-2009

Notes/Citation Information

Published in Journal of Virology, v. 83, no. 24, p. 12680-12691.

Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The copyright holders have granted the permission for posting the article here.

This article has been corrected, please see Related Content for more information.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1128/JVI.01476-09

Funding Information

This work was supported by NIH grants AI070769 and DK079293.

Related Content

Erratum, "Apolipoprotein E but Not B Is Required for the Formation of Infectious Hepatitis C Virus Particles," published in Journal of Virology, v. 84, no. 9, p. 4864.

A correction to the original article: "Volume 83, no. 24, p. 12680-12691, 2009. Page 12681, column 1, lines 9 to 7 from the bottom: 'The siRNA targeting sequences for apoB and apoE mRNAs were 5′-AGACAGAGCCGGAGCCCGA-3′ and 5′-AGACAGAGCCGGAGCCCGA-3′, respectively.' should read 'The siRNA targeting sequences for apoB and apoE mRNAs were 5′-GCAAGCAAGUUGGCAAGUA-3′ and 5′-AGACAGAGCCGGAGCCCGA-3′, respectively.'"

A PDF of this Erratum is available as Supplemental Content.

Repository Citation

Jiang, Jieyun and Luo, Guangxiang, "Apolipoprotein E but not B is Required for the Formation of Infectious Hepatitis C Virus Particles" (2009). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 68.
https://uknowledge.uky.edu/microbio_facpub/68