Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key Mechanism for the Proliferation of Epstein-Barr Virus Discovered

14.01.2010
Scientists of Helmholtz Zentrum München have elucidated a crucial mechanism in the lytic cycle of Epstein-Barr virus. A team of researchers led by Professor Wolfgang Hammerschmidt identified the function of a protein which plays a critical role in the proliferation of the virus. The Epstein-Barr virus can induce cancer. The findings, published in the current issue of the renowned journal PNAS, represent a major step forward in understanding tumor development.

The Epstein-Barr virus (EBV), a virus of the herpes family, has two distinct life phases: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active – and then induces tumor growth or promotes its synthesis in the cell. Especially in patients with weakened immune systems, EBV can cause its host cells to divide uncontrollably – causing a tumor to develop.

The causes for the transition of EBV from the quiescent phase to an active mode – particularly with respect to the responsible factors and to how the molecular mechanisms function – have until now remained elusive. With their findings, the scientists at Helmholtz Zentrum München have discovered how the virus terminates latency and activates its synthesis in the infected cells.

Professor Wolfgang Hammerschmidt, head of the Department of Gene Vectors at Helmholtz Zentrum München, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA segments are chemically modified: Some DNA building blocks carry methyl groups. They are a kind of stop signal for the cell apparatus, so that these genes cannot be converted into protein.

“BZLF1 can detect these methylation patterns in the DNA,” said Markus Kalla, lead author of the study. With its DNA binding domain, the protein binds directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. “Such a mechanism was not known before,” Wolfgang Hammerschmidt said. Previous research assumed that the methyl groups had to be removed from the DNA building blocks before the transcription factors could bind to the regulatory DNA sequence and thus activate the gene.

The researchers’ findings indicate that BZLF1 avoids this hurdle. Accordingly, BZLF1 appears to be essential for establishing and maintaining latency, but also for escaping from it.

During viral synthesis a large number of new particles are usually formed within the cell. To achieve this, viruses use large portions of the cell apparatus, in particular specific proteins and factors. After progeny synthesis the new viruses are released – researchers speak of a lytic cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen and destroys the cell supporting viral synthesis.

However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate synthesis of progeny in the infected cell, it goes into a resting phase following the infection and thus prevents a reaction of the immune system. The virus infects cells of the immune system - the so-called B cells - first inserting its DNA into their cell nucleus. Whereas most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate the DNA and to generate important structural proteins from the genes, EBV drives transformation of merely a few genes from the cell into proteins. These so-called latent genes are important for the quiescent phase: They see to it that the DNA of the Epstein-Barr virus remains stable in the cell nucleus while the cell itself proliferates. This seemingly peaceful co-existence ends when the virus goes into the lytic phase or induces tumor growth.

These findings published in PNAS by Wolfgang Hammerschmidt and his colleagues constitute an important step for a better understanding of the role of EBV in tumor growth.

Further information
Press Contact:
Sven Winkler
Head, Communications Department
Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
Phone: +49 (0) 89 3187 - 3946, Fax +49 (0) 89 3187 - 3324, e-mail: presse@helmholtz-muenchen.de
Original Publication:
Kalla, M, Schmeinck, A, Bergbauer, M, Pich, D, Hammerschmidt, W: AP-1 homolog BZLF1 of Epstein–Barr virus has two essential functions dependent on the epigenetic state of the viral genome. PNAS - Online Publication (DOI 10.1073/pnas.0911948107)

The Department of Gene Vectors of Helmholtz Zentrum München is dedicated to the molecular biological analysis of a human herpes virus, Epstein-Barr virus (EBV), and the virus’ interaction with human target cells. EBV is a pathogen which constitutes a model system for different aspects of human herpes viral infection. EBV was the first human virus to be characterized as tumor virus and is therefore considered a carcinogenic agent according to the international WHO classification. The virus is associated with a number of tumors such as nasopharyngeal carcinoma, stomach cancer, Burkitt’s and Hodgkin’s lymphoma and other human lymphomas, which most often occur in immune-suppressed patients.

Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center oriented toward Environmental Health, it focuses on chronic and complex diseases which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1700 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany’s largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 26,500 staff members.

Sven Winkler | EurekAlert!
Further information:
http://www.helmholtz-muenchen.de

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>