HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies.

The Hepatitis C virus (HCV) envelope glycoprotein E1 forms a non-covalent heterodimer with E2, the main target of neutralizing antibodies. How E1-E2 interactions influence viral fitness and contribute to resistance to E2-specific antibodies remain largely unknown. We investigate this problem using a combination of fitness landscape and evolutionary modeling. Our analysis indicates that E1 and E2 proteins collectively mediate viral fitness and suggests that fitness-compensating E1 mutations may accelerate escape from E2-targeting antibodies. Our analysis also identifies a set of E2-specific human monoclonal antibodies that are predicted to be especially resilient to escape via genetic variation in both E1 and E2, providing directions for robust HCV vaccine development.

MIP-based electrochemical sensor for direct detection of hepatitis C virus via E2 envelope protein.

Hepatitis C is the most common liver disease caused by Hepatitis C virus (HCV), and can evolve into serious health problems e.g. cirrhosis and hepatocellular carcinoma. Nowadays, the initial stage of the disease cannot be practically diagnosed, representing thus an extremely important problem of modern public health care. This study is aimed at the development of a sensor for direct detection of HCV. The sensor utilizes a synthetic recognition element prepared by the technology of molecular imprinting and representing a molecularly imprinted polymer (MIP) having molecular recognition sites of HCV envelope protein E2 (E2-MIP). E2-MIP integrated into an electrochemical sensor platform allows quantitative evaluation of binding of free E2 protein as well as HCV-mimetic particles (HCV-MPs) in human plasma with LOD value of 4.6 × 10-4 ng/mL (for HCV-MPs). The developed electrochemical HCV sensor represents a simple, fast and inexpensive alternative for the existing methods of HCV detection and paves the way for the point-of care diagnostics of Hepatitis C.

Progress in Research of the Role of Hepatitis C Virus Protein in Cell Signal Transduction Pathway / 中国实验动物学报

Abnormal cell signal transduction is associated with the occurrence and development of human diseases. Some virus pathogenicity and infection mechanism are due to virus antigen protein acting on the host cell signal transduction pathway, leading to host cell signal transduction disorder. Hepatitis C virus (HCV) is a major pathogen of chronic hepatitis C, which causes cirrhosis and hepatocellular carcinoma. But the pathogenesis of HCV and persistent infection mechanism remain far from clear. HCV pathogenesis may be related to the HCV protein expression interfering host cell signal transduction pathways. The studies of hepatitis C virus proteins acting on host cell signal transduction pathways, not only help to clarify the impact of its pathogenic mechanisms, but also benefit to new drug design and development for new treatment methods. This article summarizes the recent progress in research on the effect of hepatitis C virus protein in cell signal transduction pathways in the past few years.

The expression of protein fused HCV envelope protein E2 with His tag and its implication / 解放军医学杂志

Objective To construct the eukaryotic expression vector coding HCV gene E2 fused with His-Tag, and to express fused protein in CHO cells for investigating the function of HCV envelope protein E2. Methods The gene encoding HCV envelope protein E2 was amplified from pBRTM/HCV1-3011, a plasmid containing the cDNA of HCV's ORF, by polymerase chain reaction (PCR) method and cloned into the vector pET28(a) containing His-Tag to obtain the fused HCV envelope protein E2 gene fused with His-Tag. The fused gene was cloned into pcDNA3.1 to construct the recombinant plasmid pcDNA3.1-His-E2, which will express the E2 protein, fused with His tag. This recombinant plasmid was transfected into CHO cells by Lipofactamine 2000 reagent. The fused protein was identified by indirect immunofluorescence (IIF) and Western-blot (WB) methods. Result The positive results were obtained when the fused protein of HCV E2 with His-Tag were identified by IIF and WB methods. Conclusion The eukaryotic expression vector pcDNA3.1-His-E2 was constructed successfully and the fused proteins were expressed in cells.

SCREENING AND CHARACTERIZATION OF HUMAN PHAGE ANTIBODY TO HEPATITIS C VIRUS E2 ANTIGEN / 解放军医学杂志

To screen and characterize human phage antibody to hepatitis C virus E2 antigen. The recombinant phages were panned by HCV E2 antigen which was coated in a microwell plate. After three rounds of biopanning, 56 clones specific to HCV E2 antigen were obtained. The specificity of scFv was determined by ELISA method and cross reaction with BSA and competitive inhibition assay. HCV E2 phage antibody had a specific combination character with recombinant hepatitis C virus E2 antigen. The DNA sequence data showed that the scFv coding gene was 771bp in size