A5060225312- Hepatitis B Virus Studies
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Viral gastroenteritis research and epidemiology
- Hepatitis Viruses Studies and Epidemiology
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Toxin Mechanisms and Immunotoxins
- Pediatric Hepatobiliary Diseases and Treatments
- Virus-based gene therapy research
- Pharmacological Effects of Natural Compounds
- Liver physiology and pathology
- Cervical Cancer and HPV Research
- Global Cancer Incidence and Screening
- Organ Transplantation Techniques and Outcomes
- Chronic Disease Management Strategies
- Economic and Financial Impacts of Cancer
- Medication Adherence and Compliance
- Animal Virus Infections Studies
National Institute of Infectious Diseases
2014-2023
Nagoya University
2023
Kyushu University
2018-2021
Tokyo University of Science
2013-2019
Médecins Sans Frontières
2019
Soka University of America
2001
Hepatitis B virus (HBV) entry has been analyzed using infection-susceptible cells, including primary human hepatocytes, tupaia and HepaRG cells. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) membrane transporter was reported as an HBV receptor. In this study, we established a strain of HepG2 cells engineered to overexpress NTCP gene (HepG2-hNTCP-C4 cells). HepG2-hNTCP-C4 were shown be susceptible infection by blood–borne cell culture-derived HBV. facilitated pretreating...
Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The effect CsA was independent binding to cyclophilin and calcineurin. Rather, blockade correlated...
Sodium taurocholate cotransporting polypeptide (NTCP) is a host cell receptor required for hepatitis B virus (HBV) entry. However, the susceptibility of NTCP-expressing cells to HBV diverse depending on culture condition. Stimulation with epidermal growth factor (EGF) was found potentiate infection. Here, we show that EGF (EGFR) plays critical role in virion internalization. In EGFR-knockdown cells, or its preS1-specific fluorescence peptide attached surface, but internalization attenuated....
Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 may also carry the satellite D (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), interacts directly first 48 amino acid residues N-myristoylated N-terminal preS1 domain viral large protein3. Despite pressing need for therapeutic agents to counter HBV, structure NTCP remains unsolved. This...
Virus infection is restricted by intracellular immune responses in host cells, and this typically modulated stimulation of cytokines. The cytokines factors that determine the cell restriction against hepatitis B virus (HBV) are not well understood. We screened 36 chemokines to which were able reduce susceptibility HepaRG cells HBV infection. Here, we found pretreatment with IL-1β TNFα remarkably reduced This effect was mediated activation NF-κB signaling pathway. A cytidine deaminase,...
The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport bile acids into hepatocytes, and thus have potential to cause adverse effects. We aimed identify small molecules that inhibit HBV while maintaining transporter function.
ABSTRACT Anti-hepatitis B virus (HBV) drugs are currently limited to nucleos(t)ide analogs (NAs) and interferons. A challenge of drug development is the identification small molecules that suppress HBV infection from new chemical sources. Here, a fungus-derived secondary metabolite library, we identify structurally novel tricyclic polyketide, named vanitaracin A, which specifically inhibits infection. Vanitaracin inhibited viral entry process with submicromolar 50% inhibitory concentration...
Introduction of direct‐acting antivirals against hepatitis C virus (HCV) has provided a revolutionary improvement in the treatment outcome. In contrast to HCV, however, strategy for developing new antiviral agents B (HBV), especially viral‐targeting compounds, is limited because HBV requires only four viral genes its efficient replication/infection. Here, we identify an oligomeric flavonoid, proanthocyanidin (PAC) and analogs, which inhibit entry into host cells by targeting large surface...
Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor (EGFR) involved in NTCP-mediated viral internalization during cell process. Here, analyzed which function EGFR essential for mediating HBV internalization. In contrast to crucial EGFR-downstream signaling C (HCV), blockade proteins, including mitogen-activated protein kinase...
Sodium taurocholate cotransporting polypeptide (NTCP) is an entry receptor for hepatitis B virus (HBV) and regarded as one of the determinants that confer HBV permissiveness to host cells. However, how factors regulate ability NTCP support infection largely unknown. We aimed identify signaling regulated expression thereby HBV. Here, a cell-based chemical screening method identified Ro41-5253 decreased susceptibility infection. Pretreatment with inhibited viral process without affecting...
Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor (EGFR) involved in NTCP-mediated viral internalization during cell process. Here, analyzed which function EGFR essential for mediating HBV internalization. In contrast to crucial EGFR-downstream signaling C (HCV), blockade proteins, including mitogen-activated protein kinase...
Abstract Hepatitis delta virus (HDV) is a satellite that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as origin HDV and mechanism coevolution with helper viruses, unknown, mainly because phylogenetic gaps among deltaviruses. Here, we novel passerine birds, woodchucks, white-tailed deer by extensive database searches molecular surveillance. Phylogenetic...
Abstract Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells and thus development novel culture models for productive infection urgently needed, which will allow the study cccDNA eradication. To meet this need, we developed using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) differentiated...
Abstract Viruses exploit host factors and environment for their efficient replication. The virus-host interaction mechanisms achieving an optimal hepatitis B virus (HBV) replication have been largely unknown. Here, a single cell cloning revealed that HepAD38 cells, widely-used HBV-inducible line, contain clones with diverse permissiveness to HBV was impaired upon treatment microtubule inhibitor nocodazole, which identified as from pharmacological screening. In the microtubule-disrupted...
New diazabicyclo[2.2.2]octane derivatives, peniciherquamides A-C (1-3), and a novel herqueinone derivative, neoherqueinone (5), were isolated from fungal culture broth of Penicillium herquei. The structures these compounds determined by interpretation spectroscopic data (1D/2D NMR, MS, IR). Four known compounds, preparaherquamide (4), peniciherqueinone (6), herqueinone/isoherqueinone (7/7a), also obtained. tested for anti-hepatitis C virus (HCV) activity, peniciherquamide (3) was found to...
An efficient cell-culture system for hepatitis B virus (HBV) is indispensable research on viral characteristics and antiviral reagents. Currently, the HBV infection assay in cell culture, viruses derived from genome-integrated lines of HepG2.2.15 or HepAD-38 are commonly used. However, these not suitable evaluation polymorphism-dependent resistant mutations against obtained by transient transfection ordinary molecular clone has limited efficiencies culture.We found that an 11-amino-acid...
Current anti-hepatitis B virus (HBV) drugs are suppressive but not curative for HBV infection, so there is considerable demand the development of new anti-HBV agents. In this study, we found that fungus-derived exophillic acid inhibits infection with a 50% maximal inhibitory concentration (IC50) 1.1 µM and cytotoxic (CC50) >30 in primary human hepatocytes. Exophillic inhibited preS1-mediated viral attachment to cells did affect intracellular replication. appears target host reduce their...
Hepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, from fish to human. Hepadnaviruses their hosts have long history acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such coevolutionary "arms race" between hepadnaviruses hosts. Here, we present suggesting that the evolution sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by infection. Evolutionary analysis...
Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis patients. Antiretroviral therapy (ART) in virus/human immunodeficiency virus-1 (HBV/HIV-1)-coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss.This was a retrospective study 58 HBV/HIV-1-coinfected subjects HBsAg-positive ≥6 months before ART initiation and followed ≥1 year (median 9.9...
Interferon (IFN)-λ3 is known to have antiviral effects against various pathogens. Recently, it has been reported that the production of IFN-λ3 in colon cells after administration nucleotide analogs expected reduce hepatitis B surface antigen chronic patients. Here, we aimed prove on virus (HBV) by using an vitro HBV and infection system.We used HepG2.2.15-derived as inoculum replication-competent molecular clone a replication model.By administering HepG2 transfected with clone, core-related...
Abstract Chronic infection of hepatitis B virus (HBV) is caused by the persistence closed circular DNA (cccDNA) in nucleus infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating cccDNA remains challenging. The quantifying and understanding dynamics are essential for developing effective treatment strategies new drugs. However, it requires a liver biopsy to measure intrahepatic cccDNA, which basically not accepted because ethical aspect. We here aimed develop...
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) and 4'-ethynyl-2'-deoxyadenosine (EdA) are nucleoside analogues which inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. EdAP, a cyclosaligenyl (cycloSal) phosphate derivative of EdA, inhibits the replication influenza A virus. The common structural feature these compounds is ethynyl group at 4'-position. In this study, were prepared by synthetic strategy starting from known 1,2-di-O-acetyl-D-ribofuranose. Biological...