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Plague Debunked As Link to AIDS Immunity

Smallpox seen as likely cause of mutation

WEDNESDAY, Feb. 11, 2004 (HealthDayNews) -- New research provides more evidence that the smallpox pandemics of the Middle Ages -- and not the plague -- left generations of people equipped with a rare genetic defect that now protects them against AIDS infection.

The findings, which eliminate the plague as a contender, don't appear likely to help doctors develop better AIDS treatments. But if the mutations do turn out to provide immunity from smallpox along with AIDS, that knowledge may help bioterrorism prevention efforts, says study co-author Dr. Donald Mosier.

For now, however, the origin of AIDS immunity "is still an interesting medical mystery," says Mosier, a professor of immunology at The Scripps Research Institute in La Jolla, Calif.

An estimated 1 percent of people descended from Northern Europeans are virtually immune from AIDS infection; Swedes are most likely to be protected. Doctors first noticed the immunity in the 1980s when they discovered that some people didn't get infected even though they were repeatedly exposed to HIV, the virus that causes AIDS.

All those with the immunity share a pair of mutated genes that prevent their immune cells from developing a "receptor" that lets the virus break in. Researchers liken the receptor to a lock that viruses pick open; if the lock isn't there, the viruses can't enter.

The protection isn't absolute, however. AIDS has managed to infect a tiny number of people who share the mutation, according to Mosier. "Your risk is diminished, but it's not zero," he says.

To be born with a pair of the mutated genes, people must inherit them from both parents. About 10 percent to 15 percent of descendants of Northern Europeans have just one mutated gene, which provides limited protection against AIDS infection. Researchers have also found the mutation in Central Asians and Southern Europeans.

Experts suspect the mutation developed centuries ago and lived on through future generations, probably because those who had it lived longer and bore more children than those who didn't. But AIDS has emerged only in the modern era. "There's no evidence that anything like HIV was floating around 800 years ago," Mosier says.

Some researchers have theorized that the mutation developed and protected Northern Europeans from the plague, also known as the "Black Death." In the new study, researchers tested the theory by breeding mice with the gene mutation and trying to infect them with plague. The findings appear in a brief article in the Feb. 12 issue of Nature.

The mice got sick with plague, suggesting the mutation didn't provide any protection against the disease that killed an estimated 40 percent of Europeans around 1350 and returned two centuries later to wreak more havoc. "We eliminated one common disease as a candidate for selection," Mosier says.

The next step is to look at disease such as smallpox and perhaps cholera, he says. Researchers plan to see if the mutation protects mice from mousepox, a relative of smallpox in humans.

In a report published late last year, researchers speculated that smallpox spawned the mutation because it was always present during the Middle Ages, while the plague came and went, leaving it less of an opportunity to propagate immunity. Also, smallpox largely attacked children, potentially leaving immune people with plenty of years left to pass on the immunity to their children. Plague, by contrast, infected people of all ages.

Alison P. Galvani, one of the authors of that report and an epidemiologist at the University of California at Berkeley, says the new study is "elegant" and appears to confirm her findings.

According to Mosier, there's a chance that further research could help scientists develop better defenses against smallpox. But beyond the possible ramifications in the present, it seems the joy of solving a mystery is driving much of the research.

"With a combination of genetic techniques, mathematics and experimentation, it is possible to determine why some of our ancestors were able to leave more descendants than others," Galvani says. "I find this fascinating."

More information

Learn about bubonic plague from Brigham Young University. Get the facts about smallpox from the U.S. Centers for Disease Control and Prevention.

SOURCES: Alison P. Galvani, Ph.D., epidemiologist, Department of Integrative Biology, University of California, Berkeley; Donald Mosier, Ph.D., M.D., professor, immunology, The Scripps Research Institute, La Jolla, Calif.; Feb. 12, 2004, Nature
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