Functional Characterization of Core Genes from Patients with Acute Hepatitis C Virus Infection

Departments of Laboratory Medicine, University of Washington, Seattle, WA 98104, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 03/2010; 201(6):912-22. DOI: 10.1086/650699
Source: PubMed


The hepatitis C virus (HCV) core protein is implicated in diverse aspects of HCV-induced pathogenesis. There is a paucity of information on core in acute hepatitis C infection.
We analyzed core gene sequences and protein functions from 13 patients acutely infected with HCV genotype 1.
Although core isolates differed slightly between patients, core quasispecies were relatively homogeneous within each patient. In 2 of 4 patients studied temporally, core quasispecies did not change over time. Comparison with more than 2700 published core isolates indicated that amino acid changes from a prototype reference strain found in acute core isolates were present in chronically infected persons at low frequency (6.4%; range, 0%-32%). Core isolates associated with lipid droplets to similar degrees in Huh7 cells. Core diffusion in cells was not affected by nonconservative changes F130L and G161S in the lipid targeting domain of core. Core isolates inhibited interferon-stimulated response element- and nuclear factor kappaB-dependent transcription and tumor necrosis factor alpha-induced nuclear translocation of nuclear factor kappaB and were also secreted from Huh7 cells.
The data suggest that upon transmission, core quasispecies undergo genetic homogenization associated with amino acid changes that are rarely found in chronic infection and that, despite genetic variation, acute core isolates retain similar functions in vitro.

Download full-text


Available from: Young S Hahn, Aug 14, 2014
  • Source
    • "It has also been reported that the altered proteins in the different gts are similar, but a single amino acid change could modulate the interactions of core protein with virus and/or host proteins, strongly influencing its stability. Many of these polymorphisms may, in turn, predict RNA structures and could differentially regulate the metabolic processes that give rise to different disease conditions [43,44]. A single substitution within the HCV core-antigen sequence (A48T) reduces the sensitivity of a commonly used chemiluminescence enzyme-linked immune assay [43]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In Hepatitis C virus (HCV)-related mixed cryoglobulinemia (MCG), the non-enveloped HCV core protein (HCV-Cp) is a constituent of the characteristic cold-precipitating immune complexes (ICs). A possible correlation between HCV-Cp, virological, laboratory and clinical parameters in both untreated MCG patients and those undergoing specific treatment was explored. HCV-Cp was quantified by a fully automated immune assay. Correlations between HCV-Cp and HCV RNA, cryocrit, and virus genotype (gt) were investigated in 102 chronically HCV-infected MCG patients. HCV-Cp concentrations strongly correlated with HCV RNA levels in baseline samples. An average ratio of 1,425 IU and 12,850 IU HCV RNA per pg HCV-Cp was estimated in HCV gt-1 and gt-2 patients, respectively. This equation allowed to estimate that, on average, HCV-Cp was associated with viral genome in only 3.4% of the former and in 35% of the latter group of patients. The direct relationship between HCV-Cp and the cryocrit level suggests that the protein directly influences the amount of cryoprecipitate. Although the therapy with rituximab (RTX) as a single agent resulted in the enhancement of HCV-Cp levels, in patients treated with RTX in combination with a specific antiviral therapy (pegylated interferon-alpha plus ribavirin) the prompt and effective clearance of HCV-Cp was documented. Our data provide evidence that HCV-Cp has a direct effect on cold-precipitation process in a virus genotype-dependence in HCV-related MCG patients.
    Full-text · Article · Mar 2014 · Arthritis research & therapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this paper, a self-organizing fuzzy neural network controller (SOFNC) is design for high-speed flywheel energy storage system (FESS) to improve the transient stability and increase transfer capability of power systems. The main feature over traditional control approach lies in the model-free description of control system and parallel computing capability. Simulation results in Taiwan power system (Taipower) show that the FESS with the proposed controller has produced significant improvement in the power system performance.
    No preview · Conference Paper · Aug 2003
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV), a RNA virus belonging to the family Flaviviridae, has been considered to be a significant risk factor in HCV induced liver diseases and development of hepatocellular carcinoma (HCC). Current combination treatment of pegylated interferon-α (PEG-IFN-α) and ribavirin has shown limited efficiency, poor tolerability and significant expense mainly depending upon the HCV genotype. HCV has been divided into six genotypes and 52 subtypes present all over the world. The genetic diversity is more than 30% in different genotypes and 20% in subtypes. It has been suggested that different genotypes do vary in their infectivity and pathogenicity due to the variations in amino acid sequence, thereby influencing the rate of disease progression, severity to cirrhosis and the risk of HCC. HCV Core protein has multifunctional activities in regulation of cells growth and host genes expression essential for infectivity including apoptosis, HCV associated steatosis, immune cell functions, cell transformation, signal transduction and transcriptional regulation. Recent studies have shown variable responses for IFN-ribavirin combination therapy, steatosis, insulin resistance and HCC due to amino acid substitutions in HCV Core region of different genotypes. In the present review, we emphasize on the pathogenicity cause by HCV Core and effect of amino acid sequence variation in disease progression and HCV life cycle.
    No preview · Article · Feb 2011 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
Show more