Degradation of viral DNA in the cell nucleus opens new Hepatitis B treatment possibilities

February 21, 2014, Helmholtz Association of German Research Centres

Scientists from the Helmholtz Zentrum München and the Technische Universität München have discovered how the viral DNA of the hepatitis B virus (HBV) can be degraded in the cell nucleus of liver cells, consequently allowing the virus to be eliminated. Viruses such as HBV can persist by depositing their genetic information (DNA) in the cell nucleus, where the DNA is normally not degraded. This prevents antiviral drugs from eliminating these viruses. But the newly discovered mechanism could make this possible without damaging the infected cell in the liver. In the current issue of the prestigious journal Science, the scientists report that now new therapeutic possibilities are consequently opening up.

Although preventive vaccination is possible, the World Health Organization (WHO) reports that more than 240 million people around the world are currently suffering from a chronic hepatitis B infection. They face a high risk of developing liver cirrhosis or even liver cancer. In Germany alone, more than half a million people are affected. Although available antiviral medicines can control the hepatitis B , they cannot completely eliminate it. As a result, the HBV in the patient's liver is reactivated as soon as the treatment is discontinued.

This is due to virus DNA (cccDNA: covalently closed circular DNA) "hidden" in the . This virus DNA stores multiple copies of the virus in the nucleus of infected liver cells (hepatocytes) and in this way protects itself from destructive influences. The cccDNA serves as a template for the virus' own proteins and new viral genomes. An international team of scientists headed by Prof. Ulrike Protzer and Prof. Mathias Heikenwälder, Institute of Virology at the Helmholtz Zentrum München and the Technische Universität München, has now found a way to selectively attack and eliminate the viral genetic information in the cell nucleus of the without damaging the in the process.

"The degradation of viral DNA in the cell nucleus that we describe represents an important mechanism in the defence against the virus", Protzer reports. "Moreover, for the first time, the results offer the possibility to develop a treatment that can heal hepatitis B."

The scientists have discovered that in addition to interferons (the immune system's defence agents), activation of the lymphotoxin β receptor in the host cell promotes certain proteins and supports their function in such a way that they chemically modulate and degrade viral cccDNA. This keeps the virus from reactivating, and also prevents the disease from breaking out again, even after the treatment has ended. On the other hand, the proteins do not influence the of the host cell itself, which here is the liver cell. "With the activation of the lymphotoxin β receptor, also combined with substances that are already available, we have a very promising new therapy concept available", Heikenwälder explains.

Explore further: Novel therapeutic approaches to cure chronic HBV infection

More information: Lucifora, J. et al. (2014), "Specific and Non-Hepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA." Science, DOI: 10.1126/science.1243462

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 ...

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 ...

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 ...

Scientists identify structure of virus that could lead to hepatitis C vaccine

February 19, 2014
Rutgers University scientists have determined the structure of a hepatitis C surface protein, a finding that could assist in the development of a vaccine to halt the spread of the the deadly disease that has infected 3.2 ...

Trick that aids viral infection is identified

January 30, 2014
Scientists have identified a way some viruses protect themselves from the immune system's efforts to stop infections, a finding that may make new approaches to treating viral infections possible.

Recommended for you

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

0 comments

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.