Study shows how the herpes simplex virus reactivates in neurons.
Herpes simplex virus (HSV) is found in the brain cells of approximately 90% of the world’s population and leads to cold sores, recurrent eye infections, genital lesions, and in rare cases encephalitis. Its closely related virus, VZV, also causes chicken pox and shingles. When a person develops cold sores, the reason is that the neurons in which HSV reside, are under stress.
The lab state that the herpes virus can be reactivated even though the viral DNA in neurons is still in a repressed state. They go on to explain that the histones associated with viral DNA doesn’t undergo demethylation, a process that allows tightly packaged DNA to become more open so that gene expression can occur, which was precisely what the virus needed in order to be reactivated.
Results show that the virus has figured out a way to modify its tightly packaged DNA right next to the methyl marks, via phosphorylation of the histone adjacent to the methyl mark. The group explain that the methyl marks act as brakes to refuse gene expression, and this phosphorylation releases the brakes just enough so that a little bit of viral gene expression can occur; this is called a methyl/phospho switch. The researchers conclude that the phosphorylation was also dependent on activation of the JNK pathway and, therefore, the experiments link the stress-activated pathway to the very earliest changes to the viral DNA.
The team surmise that full viral gene expression requires removal of histone methylation, which allows the virus to complete the reactivation process, which leads to full virus formation outside the neuron. The researchers state that the next step is to establish this model of HSV infection and reactivation in human neurons, which has not yet been accomplished. They go on to add that if it can be, and if the JNK pathway is crucial for viral reactivation in humans, then it could be possible to develop treatments for the diseases that are linked to HSV.
Source: University of North Carolina School of Medicine
Categories
epigenetic methylation, epigenetic phosphorylation, epigenetics, healthinnovations, herpes, herpes simplex virus, hsv, immunology, neuroinnovations, opensource, pathogen
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