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White-Nose Research May Help AIDS Fight

Washington — In a government lab where scientists slice open dead animals to study the exotic diseases that killed them, Carol Meteyer peered through a microscope at hundreds of little bats and started to notice something very weird.

The bats had managed to survive the white-nose fungus that had killed millions of other bats hibernating in caves, mostly in the Northeast. But they had succumbed to something else that had left their tiny corpses in tatters, their wings scorched and pocked with holes.

Meteyer finally realized what had happened: In the struggle to fight off the fungus that causes white-nose syndrome, the bats were killed by their own hyperaggressive immune systems.

Meteyer, a scientist for the U.S. Geological Survey (USGS), had stumbled upon a phenomenon never before seen in mammals in the wild. A similar finding had been observed only once before — in people with AIDS.

Now scientists hope studying the immunology of bats might help in the development of treatments for AIDS.

The devastating immune-system attack, called IRIS for immune reconstitution inflammatory syndrome, plays out differently in humans and bats, according to an article by Meteyer and two colleagues that recently appeared in the journal Virulence.

When bats hibernate in winter, their heart rates slow and their immune systems all but shut down, making them vulnerable to the cave-dwelling fungus Geomyces destructans that causes white-nose and eats away skin, connective tissue and muscle.

When bats wake up in late March, their immune systems react like startled homeowners who realize prowlers are inside the house. They launch a wild search-and-destroy mission that annihilates the disease, but also healthy cells and tissue.

“It’s not natural. It’s cellular suicide. It comes out in a huge wave, going out to those areas of infection and kills everything,” said Meteyer, who was a veterinary pathologist for the USGS in Madison, Wis., at the time of her discovery but now is the deputy coordinator for contaminant biology for the agency in Reston.

For AIDS patients, the immune-system syndrome plays out differently. After antiretroviral treatment improves patients’ health, their restored immune systems can launch an exaggerated attack against any previously acquired opportunistic infection the treatment didn’t catch, causing extensive damage.

Scientists now hope to study the immunology of bats to try and uncover findings that can assist the development of treatments for AIDS.

Meteyer said she envisions a day when “we can look closely at the mechanism driving this intense response in bats and potentially get insight into this phenomenon in humans.”

Her co-author, Judith Mandl, a research fellow for the National Institutes of Health involved in AIDS research, was also intrigued by the similarities between bat and human reactions. “When you release immune suppression, you get a response that’s a lot more damaging than helpful,” she said. The third co-author is Daniel Barber, who also works at NIH.

Eleftherios Mylonakis, Virulence’s editor-in-chief, said he included the research in the Nov. 15 edition because it represents the “out of the box” thinking the journal seeks to capture. “We want to support scientists thinking in novel ways,” he said. “Very often what we see in our patients is already seen in some form or another in nature and we want to understand these connections in order to facilitate new discoveries.”

The remote possibility that an AIDS treatment can arise from the study of white-nose is about the only positive development since the bat disease was first discovered in a cave near Albany, N.Y., in 2008.

Between 5 million and 7 million bats of various species have died from the disease since that year. In Pennsylvania alone, 95 percent of little brown bats have died.

Bats have an ugly reputation as villains in books and movies, but in reality are as important as birds and bees. They pollinate plants, and a single reproductive female consumes her weight in bugs each night. A colony of 150 brown bats can eat enough adult cucumber beetles to prevent the laying of eggs that results in 33 million rootworm larvae in summer, according to a study cited by Bat Conservation International.

A 2009 study estimated that 1,320 metric tons of insect pests were not eaten because of the decline in bat numbers, requiring farmers to buy and apply more pesticides.

Meteyer started studying diseased bats in Madison when they first flew out of caves with white-nose and plopped into the yards of homeowners. Dead bats were boxed and shipped to the U.S. Fish and Wildlife Service for study.

They soon ended up in the brightly lit Necropsy Suite at the USGS National Wildlife Health Center, where Meteyer walked through two vacuum-sealed air locks, slipped on a gown, mask and surgical gloves and dissected them with razor-sharp cutting tools.

“It’s like ⅛the television show⅜ “Quincy” and some of the “CSI” programs where we’re taking samples to find out what’s going on, if it puts people at risk, if it’s new and emerging,” she said.

Scientists at the lab have studied the bird flu and other diseases so deadly that carcasses and are tossed down a drain “into an intense pressure cooker” so that they are instantly denatured and any virus is killed “before it goes anywhere,” Meter said. The air is also filtered before it leaves the building.

Meteyer has looked at more than 500 bats. At first, she checked to verify that the disease rabies was not throwing off their coordination and causing them to tear themselves apart.

Peering deeper, she noticed that their white blood cells tried to wall off the fungus. In February 2011, she read about fungal infections in animals and made the connection to IRIS while reading AIDS research that summer.

Unknown to Meteyer, Mandl had a similar revelation across the country at NIH in Bethesda. Mandl was tracking cells that disappear when the immune system is depressed, trying to figure out where they go.

Mandl recalled reading about how immune systems go into a sleep mode as animals hibernate, which led her to bats. She e-mailed one of Meteyer’s colleagues, and soon the researchers were communicating by phone and in cyberspace.

They have written several papers about bats and disease but have not met yet.

They are hoping for grants to support more research that might help bats and humans.

“You have a system set up for catastrophe,” Meteyer said, a mad army of white blood cells massed for a lethal attack. What triggers it? “They have no idea how to recognize a fungus without a chemical signal. What is the signal?”

bc-bats (TPN)