Discovery explains how cold sore virus hides during inactive phase

Now that Duke University Medical Center scientists have figured out how the virus that causes cold sores hides out, 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.

"We have provided a molecular understanding of how HSV1 hides and then switches back and forth between the latent (hidden) and active phases," said Bryan Cullen, Duke professor of molecular genetics and microbiology.

His group's findings, published in Nature, also provide a framework for studying other latent viruses, such as the chicken pox virus, which can return later in life as a case of shingles, and herpes simplex 2 virus, a genitally transmitted virus that also causes painful sores, Cullen said.

Most of the time, HSV1 lives quietly for years, out of reach of any therapy we have against it. 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," Cullen 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 new supply of viruses then travels back down the trigeminal nerve, to the site of the initial infection at the mouth. A cold sore always erupts in the same place and is the source of viruses that might infect another person, either from direct contact, or sharing eating utensils or towels, Cullen said.

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."

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.

Source: Duke University

Related stories:

What HIV needs: Identification of human factors may yield novel therapeutic targets for HIV
The Salk Institute for Biological Studies and Burnham Institute for Medical Research today announced 295 host cell factors that are involved in human immunodeficiency virus (HIV) infection. The study, published in the Oct. 3 issue of Cell, could lead to the development of a new class of HIV therapeutics aimed at disrupting the human-HIV interactions that lead to viral infection.
HIV drug maraviroc effective for drug-resistant patients
As many as one quarter of HIV patients have drug resistance, limiting their treatment options and raising their risk for AIDS and death. Now, maraviroc, the first of a new class of HIV drugs called CCR5 receptor antagonists, has been shown to be effective over 48 weeks for drug-resistant patients with R5 HIV-1, a variation of the virus found in more than half of HIV-infected patients.
New findings indicate HIV/AIDS pandemic began around 1900, earlier than previously thought
New research indicates that the most pervasive global strain of HIV began spreading among humans between 1884 and 1924, suggesting that growing urbanization in colonial Africa set the stage for the HIV/AIDS pandemic.
Capturing replication strategies used by SARS viruses in their bid to spread
Just over five years ago, an outbreak of severe acute respiratory syndrome (SARS)-coronavirus killed over 750 people. SARS (corona)virus, a positive-stranded RNA virus, replicates in the cytoplasm of host cells, attaching its replication complex to intracellular membranes that it has modified for this purpose.
Scientists identify genetic link that may neutralize HIV
Scientists from the Gladstone Institute of Virology and Immunology (GIVI) and the National Institutes of Allergy and Infectious Diseases (NIAID) have identified a gene that may influence the production of antibodies that neutralize HIV. This new information will likely spur a new approach for making an HIV vaccine that elicits neutralizing antibodies. Neutralizing antibodies, once produced in the host, can attack and checkmate an infecting virus. The research was reported in the September 5 issue of Science.
Study shows no connection between measles, mumps, rubella (MMR) vaccine and autism
In a case-control study, the presence of measles virus RNA was no more likely in children with autism and GI disturbances than in children with only GI disturbances. Furthermore, GI symptom and autism onset were unrelated to MMR vaccine timing.
New approach, old drug show promise against hepatitis C, research shows
The fight against the liver disease hepatitis C has been at something of an impasse for years, with more than 150 million people currently infected, and traditional antiviral treatments causing nasty side effects and often falling short of a cure. Using a novel technique, medical and engineering researchers at Stanford University have discovered a vulnerable step in the virus' reproduction process that in lab testing could be effectively targeted with an obsolete antihistamine.
First gene associated with dry macular degeneration found
In a study that underscores the important role that individual genetic profiles will play in the development of new therapies for disease, a multi-institutional research team – led by Kang Zhang, MD, PhD professor of ophthalmology and human genetics at Shiley Eye Center at the University of California, San Diego, School of Medicine – has made two important discoveries related to age-related macular degeneration (AMD), the leading cause of blindness in adults over the age of 60.

News discussion:

Medicine & Health news