Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

Usurping Host DNA Repair Mechanisms Enables Hepatitis B Virus to Evade Replication Inhibitors

By BiotechDaily International staff writers
Posted on 08 Jul 2013
Image: The interaction of HBV circular DNA with host UNG (uracil-DNA glycosylase), (Photo courtesy of Kanazawa University).
Image: The interaction of HBV circular DNA with host UNG (uracil-DNA glycosylase), (Photo courtesy of Kanazawa University).
A team of Japanese virologists used a duck hepatitis B virus (DHBV) model to examine the molecular pathways involved in maintaining the integrity of the virus' circular DNA (covalently closed circular DNA or cccDNA), which modulates the transition from an acute infection into a chronic disease.

The study focused on a group of enzymes called apolipoprotein B mRNA editing catalytic polypeptide (APOBEC) proteins. This family of proteins has been suggested to play an important role in innate antiviral immunity. Recently, antiviral cytidine deaminase APOBEC proteins were shown to generate uracil residues in the viral cytoplasmic nucleocapsid (NC) DNA (partially double-stranded DNA) through deamination, resulting in cytidine-to-uracil (C-to-U) hypermutation of the viral genome, which blocked viral replication. Of particular interest was the role of APOBEC3G, which had been found to interfere with HIV replication.

As uracil residues in human genomic DNA are removed by the enzyme uracil-DNA glycosylase (UNG), resulting in the creation of abasic sites that are repaired by downstream repair factors, investigators at the Kanazawa University Graduate School of Medical Science (Japan) used an avian counterpart for HBV—duck HBV (DHBV)—to investigate the affect of host UNG on viral hypermutation in cccDNA.

Results published in the May 16, 2013, online edition of the journal PLOS Pathogens revealed that the hepatitis virus was able to subvert host UNG to repair the hypermutation introduced by APOBEC3G. When UNG activity was inhibited, APOBEC3G-induced hypermutation of cccDNA was enhanced.

The investigators measured the replication ability of purified cccDNA and found that recloned cccDNA from cells expressed by both APOBEC3G and UNG inhibitor protein replicated less efficiently due to higher hypermutation rates.

Transfection experiments showed that cccDNA hypermutation was enhanced by UNG inhibition in APOBEC3G expressing cells, resulting in a significant decrease in viral production. The investigators wrote that, “We speculate that the balance between APOBECs and UNG activities on mutation frequency decides the consequence to hepadnaviruses [the viral family that includes hepatitis B]: deleterious mutations vs. diversification.”

Future research will investigate the possible role of APOBECs and host factors such as UNG in the emergence of drug-resistant strains of HBV.

Related Links:
Kanazawa University Graduate School of Medical Science




comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells (Photo courtesy of the University of Texas, Austin).

Experimental Drug Kills Cancer Cells by Interfering with Their Ion Transport Mechanism

An experimental anticancer drug induces cells to enter a molecular pathway leading to apoptosis by skewing their ion transport systems to greatly favor the influx of chloride anions. To promote development... Read more

Therapeutics

view channel
Image: Liver cells regenerated in mice treated with a new drug (right) compared with a control group (center) after partial liver removal. Healthy liver cells are shown at left (Photo courtesy of Marshall et al, 2014, the Journal of Experimental Medicine).

New Drug Triggers Liver Regeneration After Surgery

Investigators have revealed that an innovative complement inhibitor decreases complement-mediated liver cell death, and actually stimulates postsurgery liver regrowth in mice. Liver cancer often results... Read more

Lab Technologies

view channel

Genome-Wide Mutation-Searching Computational Software Designed for Genomic Medicine

Analysis software cross-references a patient’s symptoms with his genome sequence to help physicians in the diagnosis of disease. This software was created by a team of scientists from A*STAR’s Genome Institute of Singapore (GIS), led by Dr. Pauline Ng. The research findings were published August 3, 2014, in the journal... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.