Dataset Information

The Hepatitis B Surface Antigen Binding Protein: An Immunoglobulin G Constant Region-Like Protein That Interacts With HBV Envelop Proteins and Mediates HBV Entry.

ABSTRACT: Hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis, liver cancer, and liver failure, affecting 350 million people worldwide. Currently available anti-HBV drugs include (PEGylated-) interferon-? and nucleos(t)ide analogs, which can cause significant side effects and drug-resistance in many cases of long-term treatment. The lack of a reliable and robust in vitro infection system is a major barrier for understanding the HBV life cycle and discovering novel therapeutic targets. In the present study, we demonstrate that overexpression of the hepatitis B surface antigen binding protein (SBP) in HepG2 cells (HepG2-SBP) resulted in their susceptibility to HBV infection. HepG2-SBP cells supported the uptake of the viral surface protein (HBsAg-preS), HBV-pseudotyped virus, and live HBV in patient sera. Moreover, SBP-mediated HBsAg-preS uptake, and HBV pseudotyped virus infections were efficiently blocked by preS1- and SBP-specific antibodies. These observations suggest that SBP is involved in HBV entry and that HepG2-SBP cells can serve as a cellular model to study the post-binding steps of HBV infection.

SUBMITTER: Sun Y

PROVIDER: S-EPMC6167546 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Hepatitis B Surface Antigen Binding Protein: An Immunoglobulin G Constant Region-Like Protein That Interacts With HBV Envelop Proteins and Mediates HBV Entry.

Sun Yeping Y Wang Shanshan S Yi Yong Y Zhang Jing J Duan Zhongping Z Yuan Kehu K Liu Wenjun W Li Jing J Zhu Yiping Y

Frontiers in cellular and infection microbiology 20180925

Hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis, liver cancer, and liver failure, affecting 350 million people worldwide. Currently available anti-HBV drugs include (PEGylated-) interferon-α and nucleos(t)ide analogs, which can cause significant side effects and drug-resistance in many cases of long-term treatment. The lack of a reliable and robust <i>in vitro</i> infection system is a major barrier for understanding the HBV life cycle and discovering novel therapeutic ta ...[more]

PMID: 30319994

Similar Datasets

Project description:The life cycle of hepatitis C virus (HCV) is highly dependent on host cellular proteins for virus propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assay using the HCV nonstructural 5A (NS5A) protein as a probe. Of ? 9,000 human cellular proteins immobilized in a microarray, approximately 90 cellular proteins were identified as NS5A interactors. Of these candidates, Pim1, a member of serine/threonine kinase family composed of three different isoforms (Pim1, Pim2, and Pim3), was selected for further study. Pim kinases share a consensus sequence which overlaps with kinase activity. Pim kinase activity has been implicated in tumorigenesis. In the present study, we verified the physical interaction between NS5A and Pim1 by both in vitro pulldown and coimmunoprecipitation assays. Pim1 interacted with NS5A through amino acid residues 141 to 180 of Pim1. We demonstrated that protein stability of Pim1 was increased by NS5A protein and this increase was mediated by protein interplay. Small interfering RNA (siRNA)-mediated knockdown or pharmacological inhibition of Pim kinase abrogated HCV propagation. By employing HCV pseudoparticle entry and single-cycle HCV infection assays, we further demonstrated that Pim kinase was involved in HCV entry at a postbinding step. These data suggest that Pim kinase may represent a new host factor for HCV entry.Pim1 is an oncogenic serine/threonine kinase. HCV NS5A protein physically interacts with Pim1 and contributes to Pim1 protein stability. Since Pim1 protein expression level is upregulated in many cancers, NS5A-mediated protein stability may be associated with HCV pathogenesis. Either gene silencing or chemical inhibition of Pim kinase abrogated HCV propagation in HCV-infected cells. We further showed that Pim kinase was specifically required at an early entry step of the HCV life cycle. Thus, we have identified Pim kinase not only as an HCV cell entry factor but also as a new anti-HCV therapeutic target.

Dataset Information

The Hepatitis B Surface Antigen Binding Protein: An Immunoglobulin G Constant Region-Like Protein That Interacts With HBV Envelop Proteins and Mediates HBV Entry.

Publications

The Hepatitis B Surface Antigen Binding Protein: An Immunoglobulin G Constant Region-Like Protein That Interacts With HBV Envelop Proteins and Mediates HBV Entry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets