Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING
PZ HTL SA

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




Channels

Drug Discovery

view channel
Image: Chitosan is derived from the shells of shrimp and other sea crustaceans, including Alaskan pink shrimp, pictured here (Photo courtesy of NOAA - [US] National Oceanic and Atmospheric Administration).

Chitosan Treatment Clears the Way for Antibiotics to Eliminate Recurrent Urinary Tract Infections

Recurrent urinary tract infection was successfully resolved in a mouse model by treatment with the exfoliant chitosan followed by a round of antibiotics. Bacterial urinary tract infection (UTI), most... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.