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Scientists Unlock Herpes Virus' Defenses

Discovery could bring effective treatments, but more study needed

TUESDAY, July 26, 2005 (HealthDay News) -- Scientists say they've located the cellular "lock" that, so far, has barred the way to effective treatments against the herpes simplex virus.

At the same time, a separate team of researchers in Italy believe they have found the biological "key" to that lock.

"If you imagine the cell is a house with many doors or receptors, herpes can use any one of several doors to get into the cell," explained Oveta Fuller, senior author of the two papers and an associate professor of microbiology and immunology at the University of Michigan Medical School in Ann Arbor.

"Yet it has to have a particular means of getting the door open. We think we found a way to open the door," she said.

The research is interesting but has no immediate clinical application, although it does suggest future directions for the development of new drugs, said Dr. Anna Wald, an associate professor of medicine, epidemiology and laboratory medicine at the University of Washington in Seattle.

According to Fuller's team, a previously unknown receptor on the surface of most human cells, known as B5, appears to be hijacked by the virus, allowing it entry into the cell. The research team also located the gene that controls production of this receptor and detailed some of its structure. They've even developed a system to test new herpes-fighting drugs targeted at this cellular point of entry.

Their discoveries appear in two papers published recently in the Journal of Virology, which were also presented Sunday at the International Congress of Virology in San Francisco.

Unlike many other viruses, herpes can enter almost any kind of human cell and lodge there for the lifetime of the host. The virus causes genital blisters, as well as cold sores around the mouth, and can cause even more severe complications in frail individuals. Researchers are starting to suspect that the virus may also play a role in neurodegenerative disease.

About 45 million Americans suffer from genital herpes, and millions more have oral herpes. Some drugs can alleviate symptoms, but nothing eliminates the virus itself.

While the physical, emotional and social toll of the virus are well-known, less is known about how herpes exacts that toll. Most importantly, scientists have not known how the virus manages to enter cells.

"All viruses have to get across the membrane of the cell as they require the cellular machinery to reproduce themselves," Fuller said. "For over 20 years, it's been a question as to how herpes simplex does this, because it infects so many cells and lives in the body for the lifetime of the infected person."

Other viruses -- such as HIV -- infect a smaller subset of cell types so it's been relatively easy to find the molecule these pathogens use to gain entry.

Fuller and her colleagues believe that herpes uses two different receptors at once to enter a cell. One is an "attachment receptor" (to attach to the cell membrane) and one is a "fusion receptor" (allowing the virus to fuse with the cell membrane). In fact, most viruses need these two interactions (to attach and to fuse) to get into a cell, Fuller noted.

B5, the first fusion receptor ever identified, appears to be the means by which herpes simplex slips into the cell, she said.

The researchers also discovered that the B5 molecule is shaped like a "coiled coil," which might allow it to fit into the structure of some viral fusion proteins.

Coincidentally, these findings were published at the same time that a team of Italian researchers reported finding a likely "key" on the surface of the herpes virus -- one that appears to match the B5 lock identified by Fuller and her team.

"They've shown that the viral protein has the key to the lock that we found, so instead of us having to go and look for that, somebody else has shown it," Fuller said.

Now, researchers need to show that the two molecules do engage each other and then look for antagonists that will block that interaction, she said. According to Fuller, one synthetic peptide already described in the paper may do the trick.

But she cautioned that a cure for herpes infection isn't around the corner. "There's a lot to do," Fuller said. "It will take a lot of work to find something that is potent and that is specific. It will be a lot of years."

The University of Michigan holds a patent on both the system and methods used in making the discoveries.

More information

For more on genital herpes, visit the National Institute of Allergy and Infectious Diseases.

SOURCES: Oveta Fuller, Ph.D., associate professor, microbiology and immunology, University of Michigan Medical School, Ann Arbor; Anna Wald, M.D., associate professor, department of medicine, epidemiology, and laboratory medicine, University of Washington, Seattle, and medical director, Virology Research Clinic June 2005 Journal of Virology
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