Escaping Detection With an Insulator -- MEDICA - World Forum for Medicine
Picture: Herpes Simplex 
Due to an insulator the herpes
virus can go undetected for
months; © PHIL

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 defences cannot reach them, 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 at The Wistar Institute have now discovered the molecular mechanism that keeps HSV-1 activation restricted to a single gene for months or even years. They 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.

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. Not simply passive barriers, insulators help organize and regulate gene activity by marking boundaries on chromatin, the condensed genetic material that forms chromosomes.

The study also showed that HSV-1 chromatin is organized in a manner very similar to the host chromatin. Knowing what genes the virus uses to hide and re-emerge could give pharmaceutical companies targets for designing drugs that disrupt those mechanisms.; Source: Wistar Institute