Cold sores are icky. And they’re insidious. The raw, ugly blisters show up without notice and are unpreventable. Worse yet, once you’re infected with the virus that causes them, you’re stuck with it for good. But landmark research reported today by microbiologists at Duke University may offer the potential for a cure.
By age 40, nearly 90% of adults have been exposed to the herpes simplex virus-1 (HSV-1), which causes cold sores. People are usually infected as children, but many never have symptoms. For those who do, however, cold sores are a painful and permanent nuisance, always erupting in the same location, at the original site of infection on the lips or mouth. Once HSV-1 enters the body it hunkers down for life, most of the time hiding dormant in the cranial nerves near the spine. The virus can be triggered by outside stress, such as exposure to sunlight, a fever or emotional distress. After it’s active and a cold sore appears, it’s treatable with the drug acyclovir, marketed under the name Zovirax, which kills replicating HSV-1. But the mystery has been how to eliminate the virus while it’s hiding, before it produces unsightly symptoms.
Until now, research has generally concentrated on keeping HSV1 inactive — and preventing cold sores from ever showing up. But the Duke researchers took the opposite tack: figuring out precisely how to switch the virus from latency to its active stage. That’s important, says lead author Dr. Bryan Cullen, professor of molecular genetics and microbiology at Duke, “because unless you activate the virus, you can’t kill it.”
Cullen and his team were able to replicate the intricate process using lab mice. They started by identifying the tiniest components of the HSV-1 strain. In its latent stage, HSV-1 produces a single molecular product, called latency-associated transcript RNA, or LAT RNA. Unlike most messenger RNA, LAT RNA doesn’t produce proteins, so scientists have never been able to determine LAT RNA’s exact function. But by inserting the LAT RNA into mice, Cullen found that it breaks down into even smaller strands called microRNA. Researchers then discovered that it was the microRNA that blocked production of the protein that activates HSV-1. “So if there was a sufficient supply of microRNA, then the virus stayed latent,” Cullen says. “But under a high level of stress, the microRNA’s blocking mechanisms break down, thus triggering a cold sore.” The study, funded by the National Institutes of Health, will be published in the journal Nature this week.
Understanding how to override the microRNA could allow scientists to activate the virus and then kill it using acyclovir. “Once the virus sticks its head up over the fence, you whack it off for good,” Cullen says. “Yes, the person has to have one last cold sore, but it’d be worth it to most people to cure them forever.”
The theory is that by activating the virus, then preventing it from returning to hibernation, which is when researchers think it gains strength, it can be completely eradicated. Cullen believes that a drug could be developed to block the microRNA that suppress HSV-1 into latency; once it’s active, acyclovir can be used to destroy the virus permanently. Cullen suggests that this new research may also eventually be applied to other latent viruses, such as herpes simplex virus-2 (HSV-2), which causes genital herpes, or the chicken pox virus, which causes shingles in adults. Cullen warns that some patients, especially those suffering genital herpes, may have to take acyclovir on a regular basis (HSV-2 is a hardier virus), but for people with HSV-1, the virus could be eradicated with just one dose.
Cullen and his colleagues, as well as several biotech firms, are already investigating such treatments and how best to deliver them. “Are any of these viruses fatal?” Cullen says. “No. But there are a lot of people who’d be thrilled never to have a cold sore again.”