人类疱疹病毒的关键增殖机制被发现

Barr virus (EBV), a virus of the herpes疱疹 family, has two distinct清楚的，独特的 life phases阶段，时期: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active – and then induces引诱 tumor¹ growth or promotes its synthesis综合，合成 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 quiescent²静止的，沉寂的 phase to an active mode – particularly with respect to the responsible factors and to how the molecular³ mechanisms⁵ function – have until now remained elusive⁶. With their findings, the scientists at Helmholtz Zentrum München have discovered how the virus terminates latency潜伏，潜在因素 and activates⁸ its synthesis in the infected cells.

Professor Wolfgang Hammerschmidt, head of the Department of Gene⁹ Vectors at Helmholtz Zentrum München, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes¹⁰ of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA¹¹ segments are chemically modified: Some DNA building blocks carry methyl甲基，木精 groups. They are a kind of stop signal for the cell apparatus¹²装置，设备, so that these genes cannot be converted into protein.

"BZLF1 can detect these methylation甲基化 patterns in the DNA," said Markus Kalla, lead author of the study. With its DNA binding¹⁴ domain¹⁵, the protein binds¹⁶ directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. "Such a mechanism⁴ 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 bind¹³ to the regulatory DNA sequence and thus activate⁷ the gene.

The researchers' findings indicate that BZLF1 avoids this hurdle¹⁷. 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后裔，子孙 synthesis the new viruses are released – researchers speak of a lytic细胞溶素的 cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen病原体 and destroys the cell supporting viral synthesis.

However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate¹⁹ synthesis of progeny¹⁸ 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 nucleus²⁰. Whereas鉴于，反之 most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate²¹ the DNA and to generate important structural²² proteins from the genes, EBV drives transformation²³ 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 remains²⁴ stable in the cell nucleus while the cell itself proliferates²⁵. 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.