Search results for "viruses"

Hepatitis B subviral envelope particles use the COPII machinery for intracellular transport via selective exploitation of Sec24A and Sec23B

2020

Hepatitis B virus (HBV) is a leading cause of liver disease. Its success as a human pathogen is related to the immense production of subviral envelope particles (SVPs) contributing to viral persistence by interfering with immune functions. To explore cellular pathways involved in SVP formation and egress, we investigated host-pathogen interactions. Yeast-based proteomics revealed Sec24A, a component of the coat protein complex II (COPII), as an interaction partner of the HBV envelope S domain. To understand how HBV co-opts COPII as a proviral machinery, we studied roles of key Sec proteins in HBV-expressing liver cells. Silencing of Sar1, Sec23, and Sec24, which promote COPII assembly conco…

Immune Reactions in Liver Diseases

1983

Chronic hepatitis is a heterogeneous syndrome with different underlying etiologies. Viruses (hepatitis B virus, non-A, non-B viruses), drugs and even alcohol are regarded as etiological agents. A further subgroup is autoimmune-type chronic hepatitis in which an immunogenetic predisposition is of major importance. Primary biliary cirrhosis has to be separated from these subgroups of chronic hepatitis.

2014

The hepatitis B virus (HBV) is an enveloped DNA virus that replicates via reverse transcription of its pregenomic RNA (pgRNA). Budding of HBV is supposed to occur at intracellular membranes and requires scission functions of the endosomal sorting complex required for transport (ESCRT) provided by ESCRT-III and VPS4. Here, we have investigated the impact of the upstream-acting ESCRT-I and ESCRT-II complexes in HBV morphogenesis. RNA interference knockdown of the ESCRT-I subunits TSG101 and VPS28 did not block, but rather stimulate virus release. In contrast, RNAi-mediated depletion of the ESCRT-II components EAP20, EAP30 and EAP45 greatly reduced virus egress. By analyzing different steps of…

Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins.

2000

Among the three related L, M, and S envelope proteins of the hepatitis B virus (HBV), the L and S polypeptides are required for virion production. Whereas the pivotal function of the pre-S region of L in nucleocapsid envelopment has been established, the contribution of its S domain and the S protein is less clear. In this study, we evaluated the role of the cytosolic S loop, common to L and S, in HBV assembly by performing mutagenesis experiments. To distinguish between the effect of the mutations on either envelope or virion formation, we investigated the ability of the mutants to assemble into secretable subviral empty envelopes and to replace the wild-type proteins in virion maturation,…

Adefovir for lamivudine resistant HBV: More than meets the eye

2007

– In patients with LAM resistance and high levels of HBV-DNA, especially if HBeAg positive, it may be difficult to obtain a strong virological suppression with ADV. – Restrictive criteria are needed to define virological response (HBV-DNA < 10 3 copies/ml or 200 IU/ml). – Early finding of non-response or of suboptimal response after 9–12 months of ADV therapy suggests a high risk of emergence of ADV-resistant strains and should prompt a change of treatment strategy. In patients with cirrhosis, due to the risk of liver failure, treatment changes should be considered even earlier, at 3–6 months.

Myristylation is involved in intracellular retention of hepatitis B virus envelope proteins

1991

The envelope of hepatitis B virus contains three related proteins, one of which is myristylated. The nonmyristylated small and middle protein are assembled into empty envelope particles which are secreted from cells, whereas the myristylated large envelope protein is mainly found in complete virions and is not secreted in the absence of the nucleocapsid. The block to secretion can be partially overcome by mutation or deletion of the myristylation site. Creation of a myristyl attachment site in the small protein impairs the secretion of empty envelope particles but not their intracellular assembly. Myristylation may therefore play a crucial role in hepatitis B virus replication by channeling…

Mosaic particles formed by wild-type hepatitis B virus core protein and its deletion variants consist of both homo- and heterodimers.

2003

AbstractCo-expression in Escherichia coli of wild-type (wt) hepatitis B virus core protein (HBc) and its naturally occurring variants with deletions at amino acid positions 77–93 or 86–93 leads to formation of mosaic particles, which consist of three dimer subunit compositions. These compositions are wt/variant HBc heterodimers and two types of homodimers, formed by wt HBc or the variant HBc themselves. Mosaic particles were found also when both HBc deletion variants 77–93 and 86–93 were co-expressed in E. coli. These findings are discussed in terms of their significance for hepatitis B virus pathogenesis and prospective use of mosaic particles in vaccine development.

Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis.

2013

Antitumor and antiviral properties of the antimalaria drug artemisinin from Artemisia annua have been reported. Novel artemisinin derivatives (AD1-AD8) have been synthesized and evaluated using in vitro models of liver/colon cancer and viral hepatitis B and C. Cell viability assays after treating human cell lines from hepatoblastoma (HepG2), hepatocarcinoma (SK-HEP-1), and colon adenocarcinoma (LS174T) with AD1-AD8 for a short (6h) and long (72h) period revealed that AD5 combined low acute toxicity together with high antiproliferative effect (IC50=1-5μM). Since iron-mediated activation of peroxide bond is involved in artemisinin antimalarial activity, the effect of iron(II)-glycine sulfate …

Liver diseases and hepatitis B virus antigens and antibodies in chronic HBsAg carriers in childhood

1980

Liver biopsies were obtained from 109 children who had been chronic carriers of HBsAg for more than 6 months. The specimens were examined for the presen Ice of intracellular HBsAg, HBcAg and HBeAg by direct immunofluorescence. Sera were tested for HBeAg, virus B specific DNA polymerase, anti-HBs, anti-HBe and anti-HBc. On the basis of accepted histological criteria we found chronic active hepatitis (CAH) in 56 and chronic persistent hepatitis (CPH) in 19 children. 15 cases had minimal changes (minimal hepatitis, MH) and 19 normal liver tissue (healthy HBsAg carriers, HC). Children with CAH and CPH had HBeAg, DNA polymerase and anti-HBc in their serum. HBcAg and HBeAg were found in 5-50% of …

2019

Contamination of fresh water bodies by human enteric viruses from wastewater discharge is a well-established phenomenon. Here we propose a model of viral contamination of rivers based on acute gastroenteritis epidemiology and assess how well it can simulate in situ experimental monitoring. Noroviruses, rotaviruses, enteroviruses, adenoviruses and hepatitis A viruses were quantified by molecular methods after water concentration. Water flows were obtained from the Hydro databank and wastewater treatment plant (WWTP) data. Acute gastroenteritis cases based on medical prescriptions were recorded by the French public health agency. We estimated the total number of daily viral acute gastroenteri…