How Cold Sore Viruses Hide

(July 3, 2008) - Researchers say they have figured out how the virus that causes cold sores (Read about "Herpes") hides out. Now they say they may have a way to wake it up and kill it.

Cold sores, painful, unsightly blemishes around the mouth, have so far evaded a cure or even prevention. They're known to be caused by the herpes simplex virus 1 (HSV1), which lies dormant in the trigeminal nerve of the face until triggered to reawaken by excessive sunlight, fever, or other stresses. (Read about "Stress")

Most of the time, HSV1 lives quietly for years, out of reach of any therapy. It does not replicate itself during this time and only produces one molecular product, called latency associated transcript RNA or LAT RNA.

"It has always been a mystery what this product, LAT RNA, does," Bryan Cullen, one of the researchers said. "Usually viral RNAs exist to make proteins that are of use to the virus, but this LAT RNA is extremely unstable and does not make any proteins."

In studies of mice, the team showed that the LAT RNA is processed into smaller strands, called microRNAs, that block production of the proteins that make the virus turn on active replication. As long as the supply of microRNAs is sufficient, the virus stays dormant.

After a larger stress, however, the virus starts making more messenger RNA than the supply of microRNAs can block, and protein manufacturing begins again. This tips the balance, and the virus ultimately makes proteins that begin active viral replication.

The approach to curing this nuisance would be a combination therapy, Cullen said. "Inactive virus is completely untouchable by any treatment we have. Unless you activate the virus, you can't kill it," he said.

Cullen and his team are testing a new drug designed to very precisely bind to the microRNAs that keep the virus dormant. If it works, the virus would become activated and start replicating.

Once the virus is active, a patient would then take acyclovir, a drug that effectively kills replicating HSV1.

"In principle, you could activate and then kill all of the virus in a patient," Cullen said. "This would completely cure a person, and you would never get another cold sore."