Most times, the herpes simplex virus 1 (HSV1) lies dormant in the trigeminal nerve of the face. But when triggered by excessive sunlight, fever, or other stresses, it erupts into the painful, unsightly blemishes known as cold sores. The virus is common but has evaded a cure and even efforts at prevention—so far, that is.
Duke Medical Center scientists, supported by two National Institutes of Health grants, say they have figured out how the virus that causes cold sores hides out. They believe that this knowledge may yield important clues as to how to kill it.
The first step is waking up the virus. "Inactive virus is completely untouchable by any treatment we have," says Bryan Cullen, a professor of molecular genetics and microbiology. "Unless you activate the virus, you can't kill it."
While the virus is hiding out, it does not replicate itself. It produces only one molecular product, called "latency associated transcript RNA," or LAT RNA for short. "It has always been a mystery what this product, LAT RNA, does," Cullen says. "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."
But in recent studies of mice, Cullen's team showed that the LAT RNA in HSV1 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.
This finding suggests that a combination therapy may be within reach, Cullen says. He and his team are testing a new drug designed to bind precisely 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 says. "This would completely cure a person, and you would never get another cold sore."
He and the team are working with drug development companies in animal trials to begin to answer questions about how to deliver this drug most effectively.
Curing Cold Sores
October 1, 2008