Battling an Elusive Invader

By Claudia Wallis

The herpes virus perplexes researchers and defies a cure

By any measure, herpes is an extraordinary bug. "It is the ultimate parasite," declares University of Michigan Microbiologist Charles Shipman. Says Washington, D.C., Urologist Peter Gross: "If you were doing a science-fiction movie, you couldn't invent something better than herpes." What makes it unique is that unlike influenza and other viruses, it survives in the human body. long after an attack has subsided. Once herpes has found its way into your system, says Dr. Harold Kessler, a Chicago specialist in infectious disease, "it's your virus for life."

This perplexing persistence is characteristic of all five members of the human herpes family. After herpes simplex 1 and 2, the best known is the varicella-zoster virus, the cause of chicken pox, the nation's third most common ailment. Three-quarters of the U.S. population gets chicken pox by age 15. Most are never bothered by the virus again, though it will linger in their nervous systems for the rest of their lives. Some will not be so lucky. They will be victims of shingles, a painful, blistering rash that is triggered in adults when, for reasons unknown, the varicella-zoster virus reawakens.

Cytomegalovirus (CMV), another type of herpes, infects up to 80% of the U.S. popula tion, and nearly 100% of male homosexuals. Though not usually a problem for adults, CMV can be deadly to cancer patients and others whose immune systems have been suppressed by drugs. It also causes a wide range of birth defects and is the most common cause of infectious retardation in infants. Epstein-Barr virus is the herpes associated with mononucleosis. More tragically, it is believed to contribute to Burkitt's lymphoma, a cancer that mainly strikes Africans.

Herpes simplex is almost always transmitted by intimate contact between infected and noninfected skin surfaces. This does not necessarily mean sex. Notes Kessler: "If a mother has a cold sore, she shouldn't be kissing her children or anyone else." Once inside, herpes reproduces by taking over the protein-producing apparatus of the host cell. Gross calls it "a biological coup d'etat."

Once the attack has been brought under control by the immunological system, the virus retreats. In oral herpes, which is generally caused by herpes simplex Type 1, it travels through nerve fibers into the trigeminal ganglia, a group of nerve cells located near the brain. In genital herpes, usually caused by Type 2, the virus withdraws to the sacral ganglia, nerve cell clusters near the spinal cord. Lodged in the nerve cells, the herpes simplex virus is beyond the reach of the body's immune system and enters a latent stage. This stage may last forever, or it may be broken when the virus reawakens and reinfects the original site. Such recurrences may take place as often as twice a month or as rarely as once a decade.

On rare occasions, herpes in the trigeminal ganglia will journey to the brain, where it causes a generally fatal form of encephalitis. Or, in about 500,000 cases a year (including recurrences), it may follow the trigeminal nerve to the eye, provoking an infection that can seriously damage vision if left untreated. Similarly, Type 2 located in the sacral ganglia will sometimes travel to the spinal cord, producing a mild form of meningitis.

Genital herpes has also been associated with cancer of the cervix, though the evidence is inconclusive. Obscuring the issue is cervical cancer's linkage with such other factors as an early loss of virginity and a high number of sexual partners. Recently, researchers have found pieces of viral DNA in cervical tumor cells. Says Microbiologist Fred Rapp of Pennsylvania's Hershey Medical Center, "This suggests that the link is more than just statistical."

How the latent virus awakens from its slumber remains the central enigma of herpes. Dr. Abner Notkins and others of the National Institutes of Health (NIH) believe that a chemical change may cause nerve cells where the virus lurks to become "permissive" to viral replication and hence to an attack. Whatever the internal mechanism, recurrences can be triggered by sunlight, sex, menstruation and stress.

When genital herpes recurs in the final weeks of pregnancy, strict medical precautions are necessary. Herpes is lethal to up to 60% of infected newborns. For surviving babies, there is a 50% risk of blindness or brain damage. Because neonatal herpes is generally acquired during passage through an infected birth canal, a caesarean is necessary if the mother has an active infection. Los Angeles Obstetrician Lynn Yonekura, a specialist in high-risk births, recommends biweekly tests for the presence of the virus during the final trimester of pregnancy. If the tests are all negative, Yonekura believes that a vaginal delivery is safe.

The only proven treatment for genital herpes and the only one approved by the FDA is acyclovir, a creamy salve marketed by Burroughs Wellcome Co. under the trade name Zovirax. Acyclovir, which retails for about $20 a tube, works by interfering with viral replication. Applied during the initial episode of herpes, acyclovir will alleviate symptoms and speed up healing. Unfortunately, it is less effective in treating subsequent episodes and will not reduce the frequency of outbreaks. However, according to Virologist Lawrence Corey of the University of Washington, early tests of an oral acyclovir "suggest it is quite a bit more effective" than the cream. An intravenous form appears to be the best solution for acute cases of herpes.

At the University of Michigan, Dr. Charles Shipman is studying a group of compounds imposingly called acetylpyridine thiosemicarbazones, which, he says, "have a potency hundreds of times greater than that of drugs currently used." The drugs, which Shipman hopes to bring to market by 1987, do not prevent recurrences, but, he says, "they stop the lesions in their tracks."

A similar claim is made on behalf of ribavirin, a drug already marketed in 30 foreign countries by Viratek, a small West Coast firm. Ribavirin is said to interfere with the virus' reproduction by blocking protein synthesis in affected cells. Another drug sold abroad but not in the U.S. is Newport Pharmaceuticals' isoprinosine. According to Newport President Alvin Glasky, the drug "speeds up the body's natural curing process" by boosting the immune system. But so far, experts at NIH reject it as being of no proven benefit. Last week scientists at the University of Texas Health Science Center at San Antonio announced that a new experimental drug for herpes, BIOLF-62, looked promising and might be tested later this year on humans.

A different sort of treatment is being tried by Los Angeles Gynecologist Robert Scott. He has used a carbon dioxide laser to vaporize herpes lesions in 100 patients and reports a 70% success rate in preventing or delaying recurrences.

The most effective weapon against herpes would be an agent that activated the immune system before an attack. Once the virus has tunneled into the ganglia, it may be too late for a cure. "You would need a pretty remarkable drug to attack the virus genes without damaging the host cells," explains Notkins. Bernard Roizman at the University of Chicago is one of many researchers engaged in the international search for a herpes vaccine. The main challenge, he explains, is to create a substance that poses none of the dangers of the virus itself. "It can't cause cancer, for instance," he says, "and it shouldn't get into the brain." A team at the University of Birmingham in England has already tested a vaccine in 60 people who ran a high risk of contracting the disease (spouses of herpes victims). It was reportedly 100% effective for two years in preventing herpes.

"There is a Nobel Prize for the person who figures out how the viruses select their prey," says Immunologist Paul Wiesner at the Centers for Disease Control, and "a second prize for the person who can figure out the latency of the virus: Just how does it select that perfect hiding place where it can stay for years without being destroyed by the immunological system?" Atlanta Virologist Andre Nahmias, one of the two scientists who discovered Type 2 in the late 1960s, predicts that it will be another seven to ten years before researchers find a way to prevent recurrent infections. In the meantime the search is bringing about a medical revolution on the order of the breakthroughs in antibiotics in the 1940s. "Herpes is causing a boom in virology," says Corey. Ironically, victims of many kinds of infectious disease may ultimately benefit. --By Claudia Wallis. Reported by Christopher Redman/Washington and Dick Thompson/San Francisco

With reporting by Christopher Redman, Dick Thompson

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