scholarly journals Inhibition of Hepatitis B Virus Replication by the Interferon-Inducible MxA Protein

2001 ◽  
Vol 75 (6) ◽  
pp. 2684-2691 ◽  
Author(s):  
Emmanuel Gordien ◽  
Olivier Rosmorduc ◽  
Cécile Peltekian ◽  
Florianne Garreau ◽  
Christian Bréchot ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Posttranscriptional Regulation ◽  
Antiviral Effect ◽  
Complete Disappearance ◽  
Reporter System ◽  
B Virus ◽  
Host Defense System ◽  
Nucleocytoplasmic Export

ABSTRACT Human MxA is an alpha/beta interferon-inducible intracytoplasmic protein that mediates antiviral activity against several RNA viruses. We had previously shown that overexpression of the hepatitis B virus (HBV) capsid led to selective downregulation of MxA gene expression, suggesting a mechanism by which the virus escapes from the host defense system (O. Rosmorduc, H. Sirma, P. Soussan, E. Gordien, P. Lebon, M. Horisberger, C. Brechot and D. Kremsdorf, J. Gen. Virol. 80:1253–1262, 1999). In the present study, we investigated the antiviral activity of MxA protein against HBV. MxA-expressing HuH7 clones were established and transiently transfected with HBV, and viral replication was then studied. Viral protein secretion was profoundly reduced in MxA-expressing clones by 80% for HBV surface antigen (HBsAg) and 70% for HBV e antigen (HBeAg). The levels of intracytoplasmic HBsAg and HBeAg were reduced by about 80 and 50% in the two MxA-positive clones tested. A nearly complete disappearance of HBV DNA replicative intermediates was observed in MxA-expressing clones. Although the expression of total viral RNAs was not modified, two- to fourfold reductions in HBV cytoplasmic RNAs were found in MxA-expressing clones. This suggests the inhibition of HBV replication at a posttranscriptional level. Indeed, using the well-characterized posttranscriptional regulation element (PRE) reporter system, we were able to demonstrate a marked reduction (three- to eightfold) in the nucleocytoplasmic export of unspliced RNA in MxA-expressing clones. In addition, MxA protein did not interact with HBV nucleocapsid or interfere with HBV nucleocapsid formation. Our results show an antiviral effect of MxA protein on a DNA virus for the first time. MxA protein acts, at least in part, by inhibiting the nucleocytoplasmic export of viral mRNA via the PRE sequence.

scholarly journals Searching for Interferon-Induced Genes That Inhibit Hepatitis B Virus Replication in Transgenic Mouse Hepatocytes

2003 ◽  
Vol 77 (2) ◽  
pp. 1227-1236 ◽  
Author(s):  
Stefan F. Wieland ◽  
Raquel G. Vega ◽  
Rolf Müller ◽  
Claire F. Evans ◽  
Brian Hilbush ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Antigen Processing ◽  
Antiviral Effect ◽  
Small Subset ◽  
Hbv Replication ◽  
B Virus ◽  
Mouse Hepatocytes ◽  
Ifn Γ

ABSTRACT We have previously shown that alpha/beta interferon (IFN-α/β) and IFN-γ inhibit hepatitis B virus (HBV) replication noncytopathically in the livers of HBV transgenic mice and in hepatocyte cell lines derived from these mice. The present study was designed to identify transcriptionally controlled hepatocellular genes that are tightly associated with the inhibition of HBV replication and that might, therefore, mediate the antiviral effect of these cytokines. Twenty-nine genes were identified, many of which have known or potential antiviral activity. Notably, multiple components of the immunoproteasome and ubiquitin-like proteins were strongly induced by both IFN-α/β and IFN-γ, as were a number of GTP-binding proteins, including GTPases with known antiviral activity, chemokines, signaling molecules, and miscellaneous genes associated with antigen processing, DNA-binding, or cochaperone activity and several expressed sequence tags. The results suggest that one or more members of this relatively small subset of genes may mediate the antiviral effect of IFN-α/β and IFN-γ against HBV. We have already exploited this information by demonstrating that the antiviral activity of IFN-α/β and IFN-γ is proteasome dependent.

scholarly journals Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review

2014 ◽  
Vol 112 (11) ◽  
pp. 1751-1768 ◽  
Author(s):  
S. Fiorino ◽  
L. Bacchi-Reggiani ◽  
S. Sabbatani ◽  
F. Grizzi ◽  
L. di Tommaso ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Hbv Infection ◽  
Cochrane Library ◽  
Viral Pathogen ◽  
Increased Risk ◽  
B Virus ◽  
Chronic Hbv

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were ‘HBV therapy’, ‘HBV treatment’, ‘VE antiviral effects’, ‘tocopherol antiviral activity’, ‘miRNA antiviral activity’ and ‘VE microRNA’. Reports describing the role of miRNA in the regulation of HBV life cycle,in vitroandin vivoavailable studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

scholarly journals Smc5/6-antagonism by HBx is an evolutionary-conserved function of hepatitis B virus infection in mammals

2017 ◽  
Author(s):  
Fabien Filleton ◽  
Fabien Abdul ◽  
Laetitia Gerossier ◽  
Alexia Paturel ◽  
Janet Hall ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Positive Selection ◽  
Host Species ◽  
Human Hepatocytes ◽  
Arms Race ◽  
Restriction Factor ◽  
Primary Human Hepatocytes ◽  
B Virus

AbstractInfection with Hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. HBVs (family Hepadnaviridae) have been associated with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions in genome maintenance, was identified as an antiviral restriction factor of human HBV. The virus has however developed a counteraction mechanism by degrading the complex via its regulatory HBx protein. Whether the antiviral activity of the Smc5/6 complex against hepadnaviruses is an important and evolutionary-conserved function is unknown. Here, we used a combined evolutionary and functional approach to address this question. We first performed phylogenetic and positive selection analyses of the six Smc5/6 complex subunits and found that they have been highly conserved in primates and mammals. Yet, the Smc6 subunit showed marks of adaptive evolution, potentially reminiscent of virus-host “arms-race” We then functionally tested the HBx from six very divergent hepadnaviruses now naturally infecting primates, rodents, and bats. Despite little sequence homology, we demonstrate that these HBx efficiently degraded mammalian Smc5/6 complexes, independently of the host species and of the sites under positive selection. Importantly, all also rescued the replication of an HBx-deficient HBV in primary human hepatocytes. These findings point to an evolutionary-conserved requirement for Smc5/6 inactivation by HBx, showing that the Smc5/6 antiviral activity has been an important defense mechanism against hepadnaviruses in mammals. Interestingly, Smc5/6 may further be a restriction factor of other yet unidentified viruses that have driven some of its adaptation.ImportanceInfection with hepatitis B virus (HBV) led to 887000 human deaths in 2015. HBV has been co-evolving with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions, was identified as a restriction factor of human HBV antagonized by the regulatory HBx protein. Here, we address whether the antiviral activity of Smc5/6 is an important evolutionary-conserved function. We found that all six subunits of Smc5/6 have been conserved in primates with only Smc6 showing signatures of “evolutionary arms-race” Using evolutionary-guided functional assays that include infections of primary human hepatocytes, we demonstrate that HBx from very divergent mammalian HBVs could all efficiently antagonize Smc5/6, independently of the host species and sites under positive selection. These findings show that the Smc5/6 antiviral activity against HBV is an important function in mammals. It also raises the intriguing possibility that Smc5/6 restricts other, yet unidentified viruses.

Antiviral activity of Bifidobacterium adolescentis SPM0212 against Hepatitis B virus

2013 ◽  
Vol 36 (12) ◽  
pp. 1525-1532 ◽  
Author(s):  
Do Kyung Lee ◽  
Joo Yeon Kang ◽  
Hea Soon Shin ◽  
Il Ho Park ◽  
Nam Joo Ha
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Bifidobacterium Adolescentis ◽  
B Virus

Antiviral activity of 5′-O-carbonate-2′,3′-dideoxy-3′-thiacytidine prodrugs against hepatitis B virus in HepG2 2.2.15 cells

2010 ◽  
Vol 36 (6) ◽  
pp. 566-569 ◽  
Author(s):  
Dolores Gagey ◽  
Soledad Ravetti ◽  
Eliana F. Castro ◽  
María Soledad Gualdesi ◽  
Margarita C. Briñon ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
B Virus ◽  
Hepg2 2.2.15

Anti-Hepatitis B Virus Activity of New 1,2,4-Triazol-2-yl- and 1,3,4-Oxadiazol-2-yl-2-pyridinone Derivatives

2008 ◽  
Vol 63 (9-10) ◽  
pp. 667-674 ◽  
Author(s):  
Farag A. El-Essawy ◽  
Wael A. El-Sayed ◽  
Sherif A. El-Kafrawy ◽  
Asmaa S. Morshedy ◽  
Adel-H. Abdel-Rahman
Keyword(s):  
Sulfuric Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Alkylating Agents ◽  
Acid Hydrazide ◽  
Virus Activity ◽  
B Virus ◽  
Thiadiazole Derivative ◽  
High Antiviral Activity

A number of 1,3,4-oxadiazole, 3 - 9, and 1,2,4-triazole derivatives, 13 - 15, were synthesized starting form the acid hydrazide 1. The 1,3,4-thiadiazole derivative 12 was prepared from the substituted phenylthiosemicarbazide derivative 11 by treatment with sulfuric acid. The aryl hydrazone derivatives 10a - c were synthesized by reaction of the hydrazide 1 with the corresponding ketones. The thioalkyl derivatives 16a - e were prepared by akylation of the thiol derivatives 3 and 13 with different alkylating agents. The newly synthesized compounds were tested for their anti-HBV activity and some of these compounds showed high antiviral activity

scholarly journals Novel reporter system to monitor early stages of the hepatitis B virus life cycle

2015 ◽  
Vol 106 (11) ◽  
pp. 1616-1624 ◽  
Author(s):  
Hironori Nishitsuji ◽  
Saneyuki Ujino ◽  
Yuko Shimizu ◽  
Keisuke Harada ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reporter System ◽  
Early Stages ◽  
Virus Life Cycle ◽  
B Virus
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