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Key mechanism for the proliferation of Epstein-Barr virus discovered
Date:1/14/2010

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 Mnchen 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 Mnchen, 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, BZL
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Contact: Sven Winkler
presse@helmholtz-muenchen.de
49-893-187-3946
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health
Source:Eurekalert

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