Herpes simplex virus (HSV) is found in about 90 percent of the United States population and leads to cold sores, recurrent eye infections, genital lesions, and in rare cases encephalitis - inflammation of the brain which has a 30 percent mortality rate (70 to 80 percent if left untreated). Its closely related virus, VZV, also causes chicken pox and shingles.
HSV was previously found to lay dormant in neurons. Researchers an experimental assay to force the virus to go latent in mouse primary neurons in a dish and then to become reactivated. This allowed them to study specific cellular protein pathways that could be involved in viral reactivation.
They wondered whether the virus is able to sense when the neurons are under stress and activate an escape pathway. They focused on a protein called JNK, which had been linked to stress. In a dish of mouse neurons, scientists added chemicals to mimic the loss of nerve growth factor, which neurons need to remain healthy. They also used a corticosteroid - a natural stress hormone - that previously had been shown to activate the JNK pathway and trigger neuron death.
As they studied the cells, they found that the JNK protein pathway - which includes proteins called DLK and JIP3 - was activated just before the virus began to leave neurons.
When the researchers took a closer look, they found that the herpes virus can be reactivated even though the viral DNA in neurons was still in a repressed state. That is, the histones associated with viral DNA did not undergo demethylation - a process that allows tightly packaged DNA to become more open so that gene expression can occur, including HSV gene expression, which was precisely what the virus needed in order to be reactivated.
Experiments show that the virus has figured out a way to modify its chromatin - the tightly packaged DNA - right next to the methyl marks. This happens by phosphorylation of the histone adjacent to the methyl mark.
The phosphorylation was also dependent on activation of the JNK pathway. Therefore, the experiments link the stress-activated pathway to the very earliest changes to the viral DNA.
The team found that once the initial brakes are eased, full viral gene expression did require removal of the repressive histone methylation, which allows the virus to complete the reactivation process. This, in turn, leads to full virus formation outside the neuron. From there, disease states such as cold sores and encephalitis are born.
The next step is to establish this model of HSV infection and reactivation in human neurons, which has not yet been accomplished. 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, as well as its closely-related viruses.
http://news.unchealthcare.org/news/2015/december/discovery-shows-how-herpes-simplex-virus-reactivates-in-neurons-to-trigger-disease
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Limiting tumors' ability to hide from the immune system
Read more
Connecting Warburg pathway to cancer
Read more
Making prostate cancer cells run out of energy and die
Read more
How fat tissue shunts energy to tumors
Read more
Meta-analysis confirms the association between unintended weight lo…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar