Cold sore suppression

After the initial infection, the Herpes simplex 1 (HSV-1) 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.

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 neighbours. About a dozen different insulator elements have been identified in organisms as varied as yeast, fruit flies and humans.

Not simply passive barriers, insulators help organise and regulate gene activity by marking boundaries on chromatin, the condensed genetic material that forms chromosomes. By establishing chromatin boundaries, insulators can limit the range of action of other DNA elements that work to activate, or "turn on', the genes.

Recent studies on the LAT region of the HSV-1 genome have shown that nearby regions of the genome contain modifications indicative of silenced chromatin. The patterns found resemble well-studied regions where insulators are found in both yeast and chicken, namely the yeast mating loci and chicken globin locus.

The researchers now plan to study the HSV-1 insulator in mice to see how the mechanism works to block the communication of gene-activating elements such as enhancers and promoters. The group is also working to identify any additional proteins that may play a role in establishing the insulator.

Knowing what genes the virus uses to hide and re-emerge could give pharmaceutical companies targets for designing drugs that disrupt those mechanisms. The studies also have implications for treating and manipulating other types of viruses.