Significance of hepatitis B virus capsid dephosphorylation via polymerase.

Background: It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal protein, spacer, reverse transcriptase, and RNase H activities.

Methods: HBV Polymerase mutants were transfected into HuH-7 cells and assayed for replication and HBc de-P by the Phos-tag gel analysis.

Hepatitis B virus virion secretion is a CRM1-spike-mediated late event.

Background: Hepatitis B virus (HBV) is a major human pathogen worldwide. To date, there is no curative treatment for chronic hepatitis B. The mechanism of virion secretion remains to be investigated.

CRM1-spike-mediated nuclear export of hepatitis B virus encapsidated viral RNA.

Hepatitis B virus (HBV) is a global pathogen. We report here that the cellular CRM1 machinery can mediate nuclear export of entire HBV core (HBc) particles containing encapsidated viral RNAs. Two CRM1-mediated nuclear export signals (NES) cluster at the conformationally flexible spike tips of HBc particles.

A nuanced role of the small loop of hepatitis B virus small envelope protein in virion morphogenesis and secretion.

Background: The virion secretion mechanism of human hepatitis B virus (HBV) remains to be investigated. In our current study, we characterized a reverse transcriptase mutant, which changed from the YMDD motif to YMHA. We noted that this mutant YMHA secreted no virions in the medium.

Novel Naturally Occurring Mutations of Enterovirus 71 Associated With Disease Severity.

Infection with the re-emerging enterovirus 71 (EV-A71) is associated with a wide range of disease severity, including herpangina, encephalitis, and cardiopulmonary failure. At present, there is no FDA-approved therapeutics for EV-A71. Early diagnosis for the high-risk children is the key to successful patient care.

Virion Secretion of Hepatitis B Virus Naturally Occurring Core Antigen Variants.

In natural infection, hepatitis B virus (HBV) core protein (HBc) accumulates frequent mutations. The most frequent HBc variant in chronic hepatitis B patients is mutant 97L, changing from an isoleucine or phenylalanine to a leucine (L) at HBc amino acid 97. One dogma in the HBV research field is that wild type HBV secretes predominantly virions containing mature double-stranded DNA genomes.

A Polysaccharide Purified From Acts as a Potent Mucosal Adjuvant That Promotes Protective Immunity Against the Lethal Challenge With Enterovirus A71.

Enterovirus A71 (EV-A71), the pathogen responsible for the seasonal hand-foot-and-mouth epidemics, can cause significant mortality in infants and young children. The vaccine against EV-A71 could potentially prevent virus-induced neurological complications and mortalities occurring due to the high risk of poliomyelitis-like paralysis and fatal encephalitis. It is known that polysaccharide purified from (PS-G) can effectively modulate immune function.

Hypoxia and therapeutic treatment of EV-A71 with an immune modulator TLR7 agonist in a new immunocompetent mouse model.

Background: Enterovirus 71 (EV71 or EV-A71) was first identified in California about half a century ago. In recent years, outbreaks of EV-A71 were prevalent worldwide, including Taiwan, Malaysia, Singapore, Japan, and China. Between 2008 and 2011, China alone reported 1894 deaths associated with EV-A71 infection.

Persistence of Hepatitis B Virus DNA and the Tempos between Virion Secretion and Genome Maturation in a Mouse Model.

Hepatitis B virus (HBV) core protein (HBc) accumulates frequent mutations in natural infection. Wild-type HBV is known to secrete predominantly virions containing mature DNA genome. However, a frequent naturally occurring HBc variant, I97L, changing from an isoleucine to a leucine at amino acid 97, exhibited an immature secretion phenotype in culture, which preferentially secretes virions containing immature genomes.

Enterovirus 71 targets the cardiopulmonary system in a robust oral infection mouse model.

Severe infection with the re-emerging enterovirus 71 (EV71 or EV-A71) can cause cardiopulmonary failure. However, in patients' heart and lung, viral protein has not been detected. In mouse models, heart disease has not been reported.

Immunocompetent and Immunodeficient Mouse Models for Enterovirus 71 Pathogenesis and Therapy.

Enterovirus 71 (EV71) is a global health threat. Children infected with EV71 could develop hand-foot-and-mouth disease (HFMD), encephalitis, paralysis, pulmonary edema, and death. At present, no effective treatment for EV71 is available.

Adding a C-terminal Cysteine (CTC) Can Enhance the Bactericidal Activity of Three Different Antimicrobial Peptides.

The emergence of antibiotic-resistant bacteria has threatened our health worldwide. There is an urgent need for novel antibiotics. Previously, we identified a novel 37-mer antimicrobial peptide (AMP), HBcARD, with broad spectrum antimicrobial activity.

1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy.

Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells.

A Homokaryon Assay for Nucleocytoplasmic Shuttling Activity of HBV Core Protein.

Hepatitis B virus (HBV) core protein (HBc) can be present in both nucleus and cytoplasm. The arginine-rich domain (ARD) at the cytoplasmic tail of HBc contains both a nuclear localization signal (NLS) and nuclear export signal (NES). We established a homokaryon assay to detect the dynamic trafficking of HBc between nucleus and cytoplasm in hepatocytes.

HBV maintains electrostatic homeostasis by modulating negative charges from phosphoserine and encapsidated nucleic acids.

Capsid assembly and stability of hepatitis B virus (HBV) core protein (HBc) particles depend on balanced electrostatic interactions between encapsidated nucleic acids and an arginine-rich domain (ARD) of HBc in the capsid interior. Arginine-deficient ARD mutants preferentially encapsidated spliced viral RNA and shorter DNA, which can be fully or partially rescued by reducing the negative charges from acidic residues or serine phosphorylation of HBc, dose-dependently. Similarly, empty capsids without RNA encapsidation can be generated by ARD hyper-phosphorylation in insect, bacteria, and human hepatocytes.

MicroRNA miR-204 and miR-1236 inhibit hepatitis B virus replication via two different mechanisms.

Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA.

A new animal model containing human SCARB2 and lacking stat-1 is highly susceptible to EV71.

Enterovirus 71 (EV71) is a major threat to children worldwide. Children infected with EV71 could develop subclinical infection and hand-foot-and -mouth disease (HFMD). In severe cases, patients could develop encephalitis, paralysis, pulmonary edema, and death.

Control and Eradication Strategies of Hepatitis B Virus.

Hepatitis B virus (HBV) is a major human pathogen, and chronic hepatitis can lead to cirrhosis and malignant hepatocellular carcinoma. While HBV vaccine and treatment are available, it has remained a challenge to completely eradicate the virus from patients. Current therapy using either interferon or polymerase inhibitors cannot cure HBV with a high efficacy.

Improvement of in vivo antimicrobial activity of HBcARD peptides by D-arginine replacement.

We previously identified a novel antimicrobial peptide with a broad spectrum bactericidal activity from human hepatitis B virus (HBV) core protein (HBc) arginine-rich domain (ARD). We compared the antimicrobial activities of HBcARD peptides from different hepadnaviruses which share similar amino acid sequences. In general, mammalian HBcARD peptides exhibited stronger antimicrobial activity than avian peptides.

Feedback regulation of IFN-α/β signaling by Axl receptor tyrosine kinase modulates HBV immunity.

Hepatitis B virus (HBV) is known to cause age-dependent infection outcomes wherein most infections during young age result in chronicity. The mechanism underlying the differential outcome remains elusive. By using hydrodynamic injection of the replication-competent pAAV-HBV, we established a mouse model in which HBV persistence was generated in 4-5 w/o C57BL/6 young mice, but not in adult mice over 10 w/o.

MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ.

In hepatitis B virus (HBV)-replicating hepatocytes, miR-130a expression was significantly reduced. In a reciprocal manner, miR-130a reduced HBV replication by targeting at two major metabolic regulators PGC1α and PPARγ, both of which can potently stimulate HBV replication. We proposed a positive feed-forward loop between HBV, miR-130a, PPARγ, and PGC1α.