Hepatitis B virus control: Identifying proteins in mutation management

June 25, 2013

(Medical Xpress)—Researchers at Kanazawa University Graduate School of Medical Science in Japan have determined how APOBEC proteins mediate hypermutations that inhibit viral replication. They also identify the host factor protein UNG that can repair these mutations. This research is also described in the inaugural June 2013 issue of the Kanazawa University Research Bulletin.

The (HBV) is a primary cause of . So far the persistence of the virus has not been fully explained. Recently researchers showed that a group of proteins – apolipoprotein B mRNA editing catalytic polypeptide (APOBEC) proteins – were found to inhibit replication of the virus but the exact mechanism remained a mystery. Now researchers at Kanazawa University Graduate School of Medical Science in Japan have determined how APOBEC proteins mediate hypermutations that inhibit . They also identify the host factor protein UNG that can repair these mutations.

The HBV genome form is converted into stable covalently closed circular DNA (cccDNA) in the nuclei of cells when they are infected. As the authors point out, "cccDNA is not targeted by anti-HBV drugs and thus enables the re-establishment of viral replication after cessation of antiviral therapy." However the lack of an experimental system that can produce cccDNA in sufficient quantities for investigation has limited what is known about the host factors that control cccDNA.

Masamichi Muramatsu and colleagues at Kanazawa University Graduate School of Medical Science used an avian counterpart for HBV – duck HBV (DHBV) – to investigate the role of the host factor UNG in viral hypermutation in cccDNA. DHBV shares many similarities with HBV with an important advantage for experimental investigation; it reproduces cccDNA more efficiently.

Transfection experiments showed that cccDNA hypermutation was enhanced on UNG inhibition in APOBEC3G expressing cells, resulting in a significant decrease in viral production. "We speculate that the balance between AID/APOBECs and UNG activities on mutation frequency decides the consequence to hepadnaviruses: deleterious mutations vs. diversification," suggest the researchers. Their future research will look into the possible role of APOBECs and factors like UNG in the emergence of drug-resistant mutants of HBV and DHBV.

Explore further: Novel therapeutic approaches to cure chronic HBV infection

More information: Kitamura, K. et al. Uracil DNA Glycosylase Counteracts APOBEC3G-Induced Hypermutation of Hepatitis B Viral Genomes: Excision Repair of Covalently Closed Circular DNA, PLoS Pathog 9(5): e1003361. doi:10.1371/journal.ppat.1003361.

Related Stories

Novel therapeutic approaches to cure chronic HBV infection

April 25, 2013
Exciting new data presented today at the International Liver Congress 2013 include results from early in vitro and in vivo studies targeting covalently closed circular DNA (cccDNA), which may form the basis of a cure for ...

Vitamin D deficiency may help spread of hepatitis B throughout liver

June 6, 2013
Researchers from Germany have found that low levels of vitamin D are associated with high levels of hepatitis B virus (HBV) replication. Findings published online in Hepatology, a journal of the American Association for the ...

New drug stimulates immune system to kill infected cells in animal model of hepatitis B infection

April 26, 2013
A novel drug developed by Gilead Sciences and tested in an animal model at the Texas Biomedical Research Institute in San Antonio suppresses hepatitis B virus infection by stimulating the immune system and inducing loss of ...

Androgen boosts hepatitis B virus replication

February 16, 2012
Androgen enhances replication of hepatitis B virus (HBV), rendering males more vulnerable than females to this virus, according to research published in the February Journal of Virology.

New research sheds light on the molecular mechanisms by which a virus contributes to cancer

August 29, 2012
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and is associated with exposure to hepatitis B virus (HBV). Patients carrying the virus have a 100-fold greater risk of developing HCC, ...

Recommended for you

Zika virus stifles pregnant women's weakened immune system to harm baby, study finds

August 21, 2017
The Zika virus, linked to congenital birth defects and miscarriages, suppresses a pregnant woman's immune system, enabling the virus to spread and increasing the chances an unborn baby will be harmed, a Keck School of Medicine ...

Novel approach to track HIV infection

August 18, 2017
Northwestern Medicine scientists have developed a novel method of tracking HIV infection, allowing the behavior of individual virions—infectious particles—to be connected to infectivity.

Faulty gene linked to obesity in adults

August 18, 2017
Groundbreaking new research linking obesity and metabolic dysfunction to a problem in the energy generators in cells has been published by researchers from the Harry Perkins Institute of Medical Research and The University ...

Two lung diseases killed 3.6 million in 2015: study

August 17, 2017
The two most common chronic lung diseases claimed 3.6 million lives worldwide in 2015, according to a tally published Thursday in The Lancet Respiratory Medicine.

New test differentiates between Lyme disease, similar illness

August 16, 2017
Lyme disease is the most commonly reported vector-borne illness in the United States. But it can be confused with similar conditions, including Southern Tick-Associated Rash Illness. A team of researchers led by Colorado ...

Addressing superbug resistance with phage therapy

August 16, 2017
International research involving a Monash biologist shows that bacteriophage therapy – a process whereby bacterial viruses attack and destroy specific strains of bacteria - can be used successfully to treat systemic, multidrug ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.