The discovery by medical researchers of an important clue to why herpes infections stay dormant most of the time suggests it may be possible to develop a vaccine to prevent new infections and to make existing ones permanently dormant.
The research, done at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda and published in last week's New England Journal of Medicine, was done on the oral herpes virus, which causes cold sores. But preliminary evidence indicates that it applies also to the closely related virus that causes genital herpes.
The ability of the herpes virus to lie dormant for long periods and then flare up again, a phenomenon common to some other viruses, has long puzzled virologists.
It is known that although herpes viruses cause ulcerlike sores in skin, some of the viruses migrate into the body through nerves and take up permanent residence in nerve bundles called ganglia. There the virus' genes, made of DNA, enter the nucleus and behave like human genes.
When the viral genes are somehow activated, they direct the synthesis of "messenger RNA," a transcription of DNA's message which travels outside the nucleus and directs the manufacture of new herpes viruses. The new viruses travel back to the skin and make new sores.
Most of the time, however, the viral genes are dormant. Kenneth D. Croen, a medical virologist at NIAID, wondered why and speculated that if he could find out, it might suggest a strategy for keeping the virus permanently switched off.
Croen and his colleagues have discovered that the virus carries its own enforcer of dormancy in the way its DNA is built. Normally the double helix of DNA consists of two parallel strands, one containing the genetic code for a protein while the other contains a complementary but nonsense code.
The cell's apparatus for reading the genetic code acts only when a "promoter" code is in the same DNA strand. It is normally positioned just before the beginning of a true gene. The promoter tells the cell to transcribe the adjacent code into a molecule of messenger RNA. Without a promoter, the cell ignores any genetic code.
Croen's lab discovered that the nerve cells of people with herpes contain messenger RNA carrying the code not for the viral gene but for its nonsense complement. Thus when the messenger RNA for the true gene is formed, it could easily encounter the messenger RNA for the nonsense strand. Being complementary, they have an automatic tendency to bind to each other much as the complementary strands of DNA are in the double helix.
The gene in question is among the first of at least 70 genes that must be transcribed to make a new herpes virus. Unless this gene functions properly, later steps in manufacture of the virus cannot proceed.
Croen speculates that the complementary nonsense strand includes a promoter region that causes it to be transcribed into messenger RNA. As long as the promoter can work, virus production is blocked. Occasionally, Croen now thinks, something must happen to block transcription of the nonsense strand. As a result, the real gene is allowed to act, a cascade of other viral genes is activated to make new viruses and the herpes infection flares up.
The discovery suggests that it might be possible to make a vaccine that would infect human cells with a harmless virus containing the nonsense gene and a promoter that could not be blocked. Infected cells would make so much of the nonsense messenger RNA that it would swamp any viral RNA from directing the manufacture of new viruses.