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'Insulator' helps silence genes in dormant herpes virus

By adulthood, most people have suffered at least one bout of painful cold sores brought on by the Herpes simplex virus 1, also known as HSV-1. After the initial infection, the virus usually remains in the body, hiding out in nearby nerve cells where the victim's immune defenses cannot reach it, causing no symptoms at all.

In order to escape detection by the body's immune system, the latent virus works to silence genes that would cause it to replicate. In this dormant state, only a tiny fragment of the virus genome ?a single gene called the Latency-Associated Transcript gene (LAT) ?remains active. Scientists have long puzzled over the mechanism used to keep this small region of the genome going while nearby genes remain quiescent.

Now, scientists at The Wistar Institute have discovered a molecular mechanism that keeps HSV-1 activation restricted to a single gene for months or even years. The researchers have identified an "insulator" ?a stretch of DNA about 800 base pairs long ?that serves as a physical barrier between active and inactive regions of the virus genome. Base pairs are the nucleotides on each side of the rungs that connect the strands of the DNA ladder.

"By establishing an insulator in early latency, the Herpes virus can protect this one small region of the genome from silencing, allowing infected cells to survive," says study senior author Jumin Zhou, Ph.D., an associate professor at The Wistar Institute.

The findings, appearing in the May issue of the Journal of Virology, mark the first time an insulator has been identified in a virus and may lead to ways to develop strategies to manipulate the virus.

Insulators, also known as boundary elements, are DNA segments that work to prevent a gene from being influenced by the activation or repression of its neighbors. About a dozen different insulator elements have been identified in organisms as varied as yeast, fruit flies, and humans.

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Source:The Wistar Institute


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