The Prevalence and Genotype Distribution of Hepatitis C Virus in Kenya: A Systematic Review and Meta-Analysis.

Background: Hepatitis C (HCV) is a virus that causes chronic liver disease, end-stage cirrhosis, and liver cancer, yet most infected individuals remain undiagnosed or untreated. Kenya is a country located in Sub-Saharan Africa (SSA) where the prevalence of HCV remains high but with uncertain disease burden due to little population-based evidence of the epidemic. We aimed to highlight the HCV disease burden in Kenya with a summary of the available data.

Hepatitis B virus-specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV-infected hepatocytes in mice.

Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complete eradication of the virus remains a formidable challenge. Cytotoxic T lymphocytes, specific to viral antigens, either exhibit a numerical deficiency or succumb to an exhausted state in individuals chronically afflicted with HBV.

Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway.

Hepatitis B virus (HBV) infects the liver and is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Approaches for an effective cure are thwarted by limited knowledge of virus-host interactions. Herein, we identified SCAP as a novel host factor that regulates HBV gene expression.

Novel drug resistance-associated substitutions against pibrentasvir emerged in genotype 1b hepatitis C virus-infected human hepatocyte transplanted mice.

Combination therapy with glecaprevir and pibrentasvir (PIB) has high efficacy for patients with hepatitis C virus (HCV) infection except among those who experienced NS5A-P32 deletion (del) mutation during prior DAA treatment failure. However, some patients fail to achieve SVR through combination treatment even in the absence of NS5A-P32del. We analyzed emergence of NS5A resistance-associated substitutions (RASs) against PIB using HCV-infected mice.

Establishment of a novel hepatitis B virus culture system using immortalized human hepatocytes.

Recent development of hepatitis B virus (HBV) culture systems has made it possible to analyze the almost all steps of the viral life cycle. However, the reproducibility of interaction between HBV and host cells seemed inaccurate in those systems because of utilization of cancer cell lines with a difference from hepatocytes in the majority of cases. In this study, in order to resolve this point, a novel HBV culture system using non-cancer-derived immortalized human hepatocytes derived cell lines, producing exogenous human sodium taurocholate cotransporting polypeptide, was developed.

[Development of hepatitis B virus culture systems].

Recent development of hepatitis B virus (HBV) culture systems has proceeded the molecular virological studies of the life cycle of HBV including infection step. However, the reproduction of HBV life cycle under the more physiological condition may be required to know the nature of HBV more precisely. The HBV culture system, we recently developed using immortalized human hepatocytes cultured in the three dimensional condition, seemed to be one of good tools for that purpose.

Comparative study on the replication of HCV1b genome between wild-type and cell culture-adaptive mutant in regard to sensitivities against anti-HCV drugs.

The replicon system, which mimics viral genome replication in culture cells, has been widely used to analyze the genome replication of the hepatitis C virus (HCV). However, most HCV genomes used in the system include adaptive mutations (AMs) that are vital for replication in culture cells despite the nonexistence of such mutations in the genome of wild-type (WT) HCV in patients. In order to study the genome replications of WT HCV, new HCV subgenomic replicon (SGR) systems were established using Huh-7.

Identification of inhibitors of dengue viral replication using replicon cells expressing secretory luciferase.

Dengue virus (DENV) is the causative agent of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) and continues to be a public health problem in the tropical and subtropical areas. However, there is currently no antiviral treatment for DENV infection. In this study, our aim was to develop a stable reporter replicon cell system that supports constant viral RNA replication in cultured cells.

Bardoxolone methyl as a novel potent antiviral agent against hepatitis B and C viruses in human hepatocyte cell culture systems.

Antiviral drugs against hepatitis B virus (HBV) relieve symptoms experienced by patients with hepatitis; however, these drugs cannot eliminate HBV infection from all patients completely. On the other hand, direct antiviral agents (DAAs) against hepatitis C virus (HCV) can achieve near-complete elimination of HCV infection. However, recent reports have claimed that DAAs pose a risk for HBV reactivation among patients with HBV and HCV co-infection.

Efficacy of glecaprevir and pibrentasvir treatment for genotype 1b hepatitis C virus drug resistance-associated variants in humanized mice.

Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infected patients. However, the efficacy for patients who acquired potent NS5A inhibitor resistance-associated variants (RAVs) as a result of failure to respond to previous direct-acting antiviral (DAA) therapies is unclear. We investigated the efficacy of GLE/PIB treatment for genotype 1b HCV strains containing RAVs using subgenomic replicon systems and human hepatocyte transplanted mice.

Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication.

Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication.

Screening for inhibitor of episomal DNA identified dicumarol as a hepatitis B virus inhibitor.

Currently, there is no available therapy to eradicate hepatitis B virus (HBV) in chronically infected individuals. This is due to the difficulty in eliminating viral covalently closed circular (ccc) DNA, which is central to the gene expression and replication of HBV. We developed an assay system for nuclear circular DNA using an integration-deficient lentiviral vector.

Inhibitory effect of fasiglifam on hepatitis B virus infections through suppression of the sodium taurocholate cotransporting polypeptide.

Fasiglifam is a selective partial agonist of G-protein-coupled receptor 40 (GPR40), which was developed for the treatment of type 2 diabetes mellitus. However, the clinical development of fasiglifam was voluntarily terminated during phase III clinical trials due to adverse liver effects. Fasiglifam showed an inhibitory effect on sodium taurocholate cotransporting polypeptide (NTCP) in human and rat hepatocytes.

Broad-spectrum antiviral agents: secreted phospholipase A targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane.

Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM).

Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatment.

Recently, direct antiviral agents against hepatitis C virus (HCV) infection have been developed as highly effective anti-HCV drugs. However, the appearance of resistant viruses against direct anti-viral agents is an unsolved problem. One of the strategies considered to suppress the emergence of the drug-resistant viruses is to use drugs inhibiting the host factor, which contributes to HCV proliferation, in combination with direct anti-viral agents.

RNA Exosome Complex Regulates Stability of the Hepatitis B Virus X-mRNA Transcript in a Non-stop-mediated (NSD) RNA Quality Control Mechanism.

Hepatitis B virus (HBV) is a stealth virus, minimally inducing the interferon system required for efficient induction of both innate and adaptive immune responses. However, 90% of acutely infected adults can clear the virus, suggesting the presence of other, interferon-independent pathways leading to viral clearance. Given the known ability of helicases to bind viral nucleic acids, we performed a functional screening assay to identify helicases that regulate HBV replication.

Fatty acid biosynthesis is involved in the production of hepatitis B virus particles.

Hepatitis B virus (HBV) proliferates in hepatocytes after infection, but the host factors that contribute to the HBV lifecycle are poorly understood at the molecular level. We investigated whether fatty acid biosynthesis (FABS), which was recently reported to contribute to the genomic replication of hepatitis C virus, plays a role in HBV proliferation. We examined the effects of inhibitors of the enzymes in the FABS pathway on the HBV lifecycle by using recombinant HBV-producing cultured cells and found that the extracellular HBV DNA level, reflecting HBV particle production, was decreased by treatment with inhibitors suppressed the synthesis of long-chain saturated fatty acids with little cytotoxicity.

Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection.

Several viruses are known to infect human liver and cause the hepatitis, but the interferon (IFN) response, a first-line defense against viral infection, of virus-infected hepatocytes is not clearly defined yet. We investigated innate immune system against RNA viral infection in immortalized human hepatocytes (HuS-E/2 cells), as the cells showed similar early innate immune responses to primary human hepatocytes (PHH). The low-level constitutive expression of IFN-α1 gene, but not IFN-β and IFN-λ, was observed in both PHH and HuS-E/2 cells in the absence of viral infection, suggesting a particular subtype(s) of IFN-α is constitutively produced in human hepatocytes.

Thromboxane A2 synthase inhibitors prevent production of infectious hepatitis C virus in mice with humanized livers.

Background & Aims: A 3-dimensional (3D) culture system for immortalized human hepatocytes (HuS-E/2 cells) recently was shown to support the lifecycle of blood-borne hepatitis C virus (HCV). We used this system to identify proteins that are active during the HCV lifecycle under 3D culture conditions.

Methods: We compared gene expression profiles of HuS-E/2 cells cultured under 2-dimensional and 3D conditions.

PML tumor suppressor protein is required for HCV production.

PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown.

In vitro models for analysis of the hepatitis C virus life cycle.

Chronic hepatitis C virus (HCV) infection affects approximately 170 million people worldwide. HCV infection is a major global health problem as it can be complicated with liver cirrhosis and hepatocellular carcinoma. So far, there is no vaccine available and the non-specific, interferon (IFN)-based treatments now in use have significant side-effects and are frequently ineffective, as only approximately 50% of treated patients with genotypes 1 and 4 demonstrate HCV clearance.

Hepatitis C virus hijacks P-body and stress granule components around lipid droplets.

The microRNA miR-122 and DDX6/Rck/p54, a microRNA effector, have been implicated in hepatitis C virus (HCV) replication. In this study, we demonstrated for the first time that HCV-JFH1 infection disrupted processing (P)-body formation of the microRNA effectors DDX6, Lsm1, Xrn1, PATL1, and Ago2, but not the decapping enzyme DCP2, and dynamically redistributed these microRNA effectors to the HCV production factory around lipid droplets in HuH-7-derived RSc cells. Notably, HCV-JFH1 infection also redistributed the stress granule components GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1), ataxin-2 (ATX2), and poly(A)-binding protein 1 (PABP1) to the HCV production factory.

A disulfide-bonded dimer of the core protein of hepatitis C virus is important for virus-like particle production.

Hepatitis C virus (HCV) core protein forms the nucleocapsid of the HCV particle. Although many functions of core protein have been reported, how the HCV particle is assembled is not well understood. Here we show that the nucleocapsid-like particle of HCV is composed of a disulfide-bonded core protein complex (dbc-complex).