Scientists have identified a likely culprit underlying the massive and mysterious plague that has killed off tens of millions of bees in the United States over the past year. By sequencing the DNA of every microbe inhabiting the bees, researchers have pinpointed a novel virus strongly linked to infected hives. The findings could help beekeepers protect their colonies. The research also suggests an effective new method for identifying infectious pathogens, be they from bees or humans.

“This is a very significant finding,” says Dewey Caron, an entomologist at the University of Delaware, in Maryland, who was not involved in the study. “It’s not yet a smoking gun, but it really helps narrow the search.”

Over the past year, tens of millions of bees have mysteriously vanished from their hives, amounting to a loss of 50 to 90 percent of U.S. colonies. While honeybee populations have sustained several major hits to their numbers over the past century, this particular plague is unique in that adult bees seem to disappear from their hives without a trace. Because honeybees pollinate hundreds of species of fruits, vegetables, and nuts–commercial beekeepers truck their hives across the country during flowering season to pollinate crops–that loss is a major agricultural concern.

Scientists have been scrambling to find a source for the problem–known as colony collapse disorder–ever since the first case was reported in 2006. A host of possibilities have been suggested: genetically modified crops, pesticides, parasites, stress, cell phones, and even celestial intervention in the form of a honeybee rapture. But scientists now say that they are closing in on the root of the problem.

Using new, rapid gene-sequencing methods, scientists from Columbia University, Pennsylvania State University, and the U.S. Department of Agriculture (USDA) analyzed DNA from both healthy and infected bee colonies, along with the viruses, bacteria, and fungi that colonize them–an approach known as metagenomics. (See “Sequencing in a Flash” and “Our Microbial Menagerie.”) After subtracting out bee DNA sequences–identified with the aid of the recently released honeybee genome–scientists were left with microbial DNA. They found that one particular virus, known as Israeli acute paralysis virus of bees, was found only in colonies that suffered significant losses. In a follow-up study of 51 bee colonies from across the country–30 diseased colonies and 21 healthy ones–all but one colony infected with Israeli acute paralysis virus also had colony collapse disorder. In other words, the virus could predict collapse 96 percent of the time. The findings are published today online in the journal Science.

While the results are exciting, scientists caution that it’s too soon to say whether the virus truly triggers the disorder. “We still have a great deal of research to do to figure out why honeybees are dying in the U.S.,” says Jeffery Pettis, an entomologist at the USDA, in Beltsville, MD, who was involved in the research.

Autopsies performed soon after the first reports of the problem revealed that bees from collapsed colonies had signs of multiple infections, suggesting that the virus may act in conjunction with other stressors, such as parasitic mites. “Mites are a major source of bee mortality,” says Diana Cox-Foster, an entomologist at Pennsylvania State University who led the new study and has previously shown that the parasites can immunosuppress bees. “That might weaken the bee and cause amplification of other pathogens or the virus.” To determine exactly how these different factors interact, Cox-Foster and her collaborators are now planning controlled studies in which they will expose bees to both the virus and a series of other stressors, such as mites and pesticides.

The virus, first identified in Israel in 2004, is from a poorly studied class of insect-infecting viruses. While it has been detected in bee colonies in Israel and Australia, those countries haven’t reported the same set of symptoms associated with colony collapse disorder in the United States. Scientists think the virus may have mutated after entering the country. “We know from other viruses like West Nile that very small genetic changes can turn a benign virus into virulent ones,” says Edward Holmes, a biologist at Penn State who was also involved in the study. “It’s quite possible that very small genetic changes that we haven’t yet characterized may make the virus behave differently in Israel, Australia, and the USA.”

The researchers say that their findings also direct them to a potential point of entry for the virus. All diseased hives tested were either imported from Australia or had been in contact with Australian bees, and the earliest signs of colony collapse were seen in 2004, the first year that honeybees were imported from Australia. “This is a real cautionary note,” says Caron. “I think it tells us we have to take a longer look at importation of stock.” As demand for honeybee-pollinated crops, most notably almonds, has grown, so has the need for bees, resulting in a boost in importation into the United States. According to the USDA’s Pettis, researchers are in talks with the department’s Animal and Plant Health Inspection Service and with Australian authorities to determine if importation from Australia should be banned or subjected to more-intensive screening.

If the virus does turn out to be the primary trigger of colony collapse, scientists say that the best near-term preventative measure is keeping hives healthy. While beekeepers do medicate bees for mite and bacterial infections, “we don’t have treatments for viral infections,” says Cox-Foster. “If you have colonies that have died, don’t reuse the equipment. Keep the bees as healthy as possible. Keep them well fed, and minimize stress. And keep down other pathogens–in particular, mites.” Beekeepers can also irradiate infected equipment.

In the long term, scientists may be able to breed bees that are resistant to the virus. The Israeli researcher who initially identified the virus also found that some bees appeared to be immune: these bees were found to have a small piece of the viral DNA integrated into their genome. “It’s equivalent to a naturally occurring resistant bee,” says W. Ian Lipkin of Columbia University, in New York, who led the metagenomics arm of the current study. Scientists have already bred bees more resistant to mites and other factors.

The new study was Lipkin’s first foray into the insect world. An epidemiologist who helped uncover the pathogen underlying West Nile virus, Lipkin was recruited by Cox-Foster to help find the source of the mysterious bee disease after he gave a talk on his approach last year. He says that the metagenomics methods he and his colleagues used laid out a “road map for vigorously investigating outbreaks of infectious disease.” Previously, scientists investigating an infectious-disease outbreak would approach the problem with a particular culprit in mind and then laboriously try to grow and characterize the microbes. “With this approach, we can investigate everything that might be associated with a given disease,” says Lipkin. In the case of a virus like SARS, he says, “instead of spending months working out ways to culture the virus, we could get results in as little as a week.”