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.
From: "Key Mechanism for the Proliferation of Epstein-Barr Virus Discovered."
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