Small RNA fragments derived from multiple RNA classes - the missing element of multi-omics characteristics of the hepatitis C virus cell culture model.

Background: A pool of small RNA fragments (RFs) derived from diverse cellular RNAs has recently emerged as a rich source of functionally relevant molecules. Although their formation and accumulation has been connected to various stress conditions, the knowledge on RFs produced upon viral infections is very limited. Here, we applied the next generation sequencing (NGS) to characterize RFs generated in the hepatitis C virus (HCV) cell culture model (HCV-permissive Huh-7.

RNA-Seq-based analysis of differential gene expression associated with hepatitis C virus infection in a cell culture.

Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.

Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice.

Background: Fusion of Hepatitis B virus surface antigen (HBsAg) to a DNA construct might be considered as a strategy to enhance cellular and cytotoxic T-lymphocytes (CTL) responses of a Hepatitis C Virus core protein (HCVcp)-based DNA vaccine comparable to that of adjuvanted protein (subunit) immunization.

Materials And Methods: pCHCORE vector harboring coding sequence of HBsAg and HCVcp (amino acids 2-120) in tandem within the pCDNA3.1 backbone was constructed.

Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.

Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes.

Lipoprotein lipase inhibits hepatitis C virus (HCV) infection by blocking virus cell entry.

A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL) biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants.

Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice.

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection.

The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a.

Evaluation of core and NS4B synthetic peptide-based immunoassays for the detection of hepatitis C virus antibodies in clinical samples from Cameroon, Central Africa.

Background: According to previous data, the antibodies produced during natural hepatitis C virus (HCV) infection frequently recognize amino acids 10-43 in the core protein and 1689-1740 or 1921-1940 in the non-structural 4B (NS4B) protein. The reactivity of these peptides with the corresponding antibodies has mainly been evaluated using serum samples from Western countries where HCV genotype 1 (HCV-1) is predominant, and no information is available concerning samples from sub-Saharan countries where high HCV variability has been reported. OBJECTIVE OF THIS STUDY: To evaluate the performance of HCV core and NS4B peptide-based immunoassays in the serodiagnosis of HCV infection in Cameroon subjects.

Hepatitis C virus controls interferon production through PKR activation.

Hepatitis C virus is a poor inducer of interferon (IFN), although its structured viral RNA can bind the RNA helicase RIG-I, and activate the IFN-induction pathway. Low IFN induction has been attributed to HCV NS3/4A protease-mediated cleavage of the mitochondria-adapter MAVS. Here, we have investigated the early events of IFN induction upon HCV infection, using the cell-cultured HCV JFH1 strain and the new HCV-permissive hepatoma-derived Huh7.

Mechanism of cell infection with hepatitis C virus (HCV)--a new paradigm in virus-cell interaction.

Hepatitis C virus (HCV) is an enveloped, single-stranded RNA virus, belonging to the Flaviviridae family. HCV infection is a major cause of chronic hepatitis worldwide, leading to steatosis, liver cirrosis and hepatocellular carcinoma. Significant advances in understanding the mechanisms of HCV infection have been made since the development of a cell culture system reproducing the complete HCV cell cycle in vitro.

Initiation of hepatitis C virus infection requires the dynamic microtubule network: role of the viral nucleocapsid protein.

Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in the initiation of productive HCV infection. Microtubules were required for virus entry into cells, as evidenced using virus pseudotypes presenting HCV envelope proteins on their surface.

Hepatitis C virus cell entry: role of lipoproteins and cellular receptors.

Hepatitis C virus (HCV), a major cause of chronic liver disease, is a single-stranded positive sense virus of the family Flaviviridae. HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Tetraspanin CD81, human scavenger receptor SR-BI, and tight junction molecules Claudin-1 and occludin are the main receptors that mediate HCV entry.

Hepatitis C virus core protein induces lipid droplet redistribution in a microtubule- and dynein-dependent manner.

Attachment of hepatitis C virus (HCV) core protein to lipid droplets (LDs) is linked to release of infectious progeny from infected cells. Core progressively coats the entire LD surface from a unique site on the organelle, and this process coincides with LD aggregation around the nucleus. We demonstrate that LD redistribution requires only core protein and is accompanied by reduced abundance of adipocyte differentiation-related protein (ADRP) on LD surfaces.

Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection.

The host-virus interactions leading to cell infection with hepatitis C virus (HCV) are not fully understood. The tetraspanin CD-81 and human scavenger receptor SR-BI/Cla1 are major receptors mediating virus cell entry. However, HCV in patients' sera is associated with lipoproteins and infectious potential of the virus depends on lipoproteins associated to virus particles.

Fc gamma receptor-like hepatitis C virus core protein binds differentially to IgG of discordant Fc (GM) genotypes.

Immunoglobulin GM allotypes are associated with the outcome of several infections, including hepatitis C virus (HCV) infection, but the underlying mechanisms are not known. HCV employs sophisticated strategies to evade host immunosurveillance. One such strategy might involve the scavenging of the Fc gamma domain of the anti-HCV IgG antibodies by its Fc gamma receptor-like site formed by HCV core protein, potentially interfering with the Fc gamma-mediated host defense mechanisms.

HCV core protein immunization with Montanide/CpG elicits strong Th1/Th2 and long-lived CTL responses.

An efficient vaccine against Hepatitis C virus (HCV) infection requires induction of strong humoral and cellular responses against viral proteins. We evaluated the immunogenicity of HCV core protein (HCVcp), a prime vaccine candidate, formulated in various human compatible adjuvants. An Escherichia coli-expressed HCVcp, purified in native conditions was used for murine immunization in separate groups of: free HCVcp (Ag), Ag+C/IFA (Freunds), Ag+CpG, Ag+M720 (Montanide ISA 720), Ag+F127 (Pluronic acid) and cocktails of Ag+F127+CpG and Ag+M720+CpG.

Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site.

A direct involvement of the PreS domain of the hepatitis B virus (HBV) large envelope protein, and in particular amino acid residues 21 to 47, in virus attachment to hepatocytes has been suggested by many previous studies. Several PreS-interacting proteins have been identified. However, they share few common sequence motifs, and a bona fide cellular receptor for HBV remains elusive.

The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins.

The possible role of candidate receptors in the cellular penetration of HCV from serum of infected patients remains unclear. SR-BI/Cla1 interacts with plasma HDL, native and modified LDL, and VLDL, and facilitates cellular cholesterol efflux to lipoprotein acceptors. SR-BI/Cla1 binds HCV E2 protein and interacts with HCV pseudotypes via the HVR1 of the E2 envelope glycoprotein.

Hepatitis C virus particles and lipoprotein metabolism.

The majority of infectious hepatitis C particles are present in the low-density fractions from plasma of infected patients, suggesting an association of the virus with lipoproteins and the use of lipoprotein receptors for cell entry. Although classical hepatitis C virus (HCV) virions have been reported by some investigators, their role in the HCV life cycle has not been clearly identified. Moreover, two other forms of particles have been characterized: low-density lipo-viro-particles (LVPs) and high-density particles.

Fcgamma receptor-like activity of hepatitis C virus core protein.

We have previously demonstrated that viral particles with the properties of nonenveloped hepatitis C virus (HCV) nucleocapsids occur in the serum of HCV-infected individuals (1). We show here that nucleocapsids purified directly from serum or isolated from HCV virions have FcgammaR-like activity and bind "nonimmune" IgG via its Fcgamma domain. HCV core proteins produced in Escherichia coli and in the baculovirus expression system also bound "nonimmune" IgG and their Fcgamma fragments.

Structural and functional characterization of a monoclonal antibody specific for the preS1 region of hepatitis B virus.

The monoclonal antibody 5a19, raised against the ay serotype of hepatitis B virus, binds to the segment of the preS1 region comprising residues 37-43, which is implicated in attachment of the virus to hepatocytes. The dissociation constant, derived from kinetic studies using surface plasmon resonance techniques, is in the low nanomolar range. The nucleotide sequence of the variable domains has been determined and the corresponding germ-line genes have been identified.