Science looks before viruses leap

What a semi-nomadic ethnic group — and their performing monkeys — can teach us about how viruses jump from animals to humans
Dr. Sharmin Akhtar, an anthropologist, interviews a Bedey man as part of a research project.
Dr. Sharmin Akhtar (left), an anthropologist and zoologist at Jahangirnagar University in Savar, Bangladesh, interviews a Bedey man as part of a research project to understand how viruses jump from monkeys to humans. He is a member of a semi-nomadic ethnic group that travels throughout Bangladesh giving performances with trained monkeys. Photo by Lynn Johnson

Dr. Lisa Jones-Engel was en route to the Bangladeshi village of Dhamrai with her research team when she saw a man in his early 30s, walking down the side of the dusty road and carrying a canvas bag, who would change the direction of her work for the next nine years.

The University of Washington primatologist yelled to her colleagues to stop the van. They pulled over and Jones-Engel jumped out.

Trailing behind the man was monkey on a lead. Jones-Engel immediately knelt down to make friends with the macaque. The animal’s owner was a member of the Bedey people, a semi-nomadic group that travels around Bangladesh and the surrounding countries, giving performances for cash with their trained (but, Jones-Engel pointed out, never fully domesticated) monkeys.

This Bedey performer and others like him would soon add a curious wrinkle to the researchers’ decades-long search to understand how viruses leap from monkey to human. In short, even though nearly all the Bedey-owned macaques the researchers tested carry a virus called simian foamy virus, which is known to pass easily to humans, none of the 45 ethnic Bedey people tested to date have been infected.

“Once we found these folks, this lightbulb went off in my head. My spidey sense was tingling,” Jones-Engel said. She knew the Bedey were going to play a role in her research, somehow.

Why study a harmless virus?

Jones-Engel is the eyes and ears on the ground in Bangladesh, leading a team of field researchers that collects information, blood and saliva from macaques and humans to understand those infectious leaps, otherwise known as zoonoses. Back in Seattle, the samples they collect are analyzed by virologists at Fred Hutchinson Cancer Research Center under the leadership of Dr. Maxine Linial.

Linial is an expert in the vividly named foamy virus, so-called because when they infect and kill cells in a petri dish, the whole dish looks like a miniature bubble bath. But despite their dramatic infectious tendencies in the lab, foamy viruses have never been known to kill or even harm a healthy animal. While humans can catch simian foamy virus from monkeys (there’s no human version of foamy virus), it has never been seen to pass from human to human. It doesn’t cause diseases in people either. But it’s always possible that could change.  

The most common and dangerous strain of HIV, responsible for the vast majority of the world’s HIV infections, arose from a single transmission event between a chimpanzee and an African hunter. Retroviruses, the class of virus that includes both HIV and foamy viruses, are constantly and quickly evolving. The simian version of HIV actually originated in monkeys, but the virus doesn’t make them sick. It wasn’t until two different types of that virus recombined, or mingled their genetic material, in the body of a chimpanzee who’d dined on the monkeys that the virus mutated in such a way as to more easily pass to humans.

“We know foamy viruses mutate very frequently,” Linial said. “The potential is there for creation of new ones. Fortunately, nothing has been seen.”

Linial has been studying foamy viruses for nearly 25 years because of that potential and because of HIV’s history — almost nobody studies animal viruses before they start killing humans, Linial said. But maybe we should.

“Nobody studied Ebola when it was just a bat virus, but as soon as humans start dying everyone jumps in,” she said. “I think it’s better to know about viruses before they become highly pathogenic.”

While zoonotic infections are common, the overwhelming majority do not lead to pandemics or viruses able to pass from human to human, as HIV does. But there’s always the potential for more jumps from animals to people and, if these viruses take hold in the new host, for the emergence of pandemics on the level of HIV or Ebola.

Foamy viruses are not pathogenic (disease-causing) — at least not yet — but they’re everywhere. Nearly every wild adult monkey and ape tested for simian foamy virus, the nonhuman primate form of the virus, comes up positive. And lots of animals from all over the world have been tested, Linial said. 

Dr. Lisa Jones-Engel (right) meets a performing Bedey monkey
Dr. Lisa Jones-Engel (right), a primatologist at the University of Washington, meets a performing Bedey monkey named Madhu (the Bengali word for honey). Photo by Lynn Johnson

When humans move into monkey territory

To understand more about how foamy viruses pass from monkeys to people, Linial joined forces with Jones-Engel nearly 10 years ago. At the time, the primatologist was traveling throughout Asia studying viruses that jump the other way, from humans to monkeys.

In the course of her studies, Jones-Engel soon realized that of all the Asian countries, Bangladesh was a prime location to study infections shared between people and animals. It’s one of the most densely populated countries in the world, as well as home to 10 different species of primates. One type of monkey in particular, the rhesus macaque, has adapted incredibly well to living in urban environments, Jones-Engel said.

“This is the monkey that will triumph,” she said. “When all else fails, macaques will inherit the earth. These animals are really good at living side by side with humans.”

With so many macaques living in close proximity to so many humans, Bangladesh is a ripe breeding ground for zoonotic infections, the researchers found.

“We knew this was a really interesting interface,” Jones-Engel said. “You have all these urbanized monkeys, you have all these villagers, you have all these people in Bangladesh. The potential for the zoonotic transmission of SFV [simian foamy virus] should be very high. And it was.”

Foamy virus is primarily passed from monkey to monkey or from monkey to human via saliva. These macaques aren’t cuddling up to their human neighbors for a sloppy kiss — they bite. Fully-grown macaques weigh between 15 to 20 pounds and are incredibly strong, said Jones-Engel, who’s been bitten herself in the course of her studies (but tests negative for foamy virus).

Since 2006, the researchers have surveyed and collected samples from 350 Bangladeshi macaques and 269 adult Bangladeshi village residents, about 45 percent of whom reported being bitten. And 17 of those villagers tested positive for foamy virus in the virologists’ assays. That’s a very high infection rate, Linial noted, the highest of any known simian zoonotic infection.

In a study published in 2013 in the journal Emerging Microbes and Infections, Jones-Engel, Linial and their colleagues reported those findings. They also showed that humans can be infected with multiple strains of the virus — strains that could genetically mingle, as the HIV precursor did. Some of those strains jump more easily to humans, Linial said.

‘What’s different about the Bedey?’

Along the way, spurred by her first encounter with the Bedey man she saw on the side of the road, Jones-Engel and her team gathered samples and information from as many Bedey people and their trained macaques as they could gain access to. The researchers were eager for those results.

“I figured these guys were going to be the ones just bubbling over with foamy virus,” Jones-Engel said. “I mean, how could they not be? From birth, they are raised with these animals. They are bitten, scratched, peed on, pooped on, they share food, they share their tents, they groom together.”

But they weren’t.

It wasn’t easy for the research team to gain reliable access to the Bedey. They’re generally suspicious of outsiders, and with good reason, Jones-Engel said: The Bedey are marginalized and often actively persecuted in Bangladesh.

They’re also not easy to track down. The nomads travel from village to village, using the trained monkeys, which are sometimes decorated with paint, to put on simple performances. The performers then move on once they’ve collected donations from the crowd.

Jones-Engel was able to gain their trust in part because of her unique approach to the traveling family groups, of which researchers estimate there are 10,000 in Bangladesh. “I go in via the monkey,” she said. “The first thing I do is just sit down and start making friends with the monkeys. I think they’re so astonished by that because most people don’t like monkeys. … I really just love monkeys.”

Jones-Engel collaborates with several researchers from the Department of Zoology at Jahangirnagar University in Savar, Bangladesh, who helped the American scientists make contact with the Bedey. Jones-Engel and her team of veterinarians, physicians and animal technicians also offered basic veterinary care for the monkeys. And the Bedey were grateful, she said. The families depend on their trained animals for their livelihood but don’t traditionally have access to health care for themselves or the monkeys.

Still, it took Jones-Engel and her team years to gain the Bedey people’s trust to the point that they could collect a decent number of samples. They still don’t have as many as they’d like, but the data they do have point in a surprising direction.

Of the 45 adult Bedey from six different traveling groups the researchers sampled, nearly 90 percent reported being bitten in their lifetimes (far more than the average Bangladeshi villager). And the bites often leave significant scars. Only one Bedey out of those 45 tested positive in an initial assay for an immune response to foamy virus, but when the researchers followed up with a more sensitive test looking for the virus’ genetic material in the blood, that test came up negative. The second test is a more accurate assay for a true infection, Linial said, while the first test may just indicate exposure to the virus.

“When the data first started trickling in I thought it was just an anomaly,” Jones-Engel said. “If any group should have been positive, I would have put my money on the Bedey.”

Linial, Jones-Engel and their colleagues reported these results in the Journal of Virology in April.

“I don’t want to say [they’re] resistant, but we just have no evidence that they are persistently infected,” Linial said, noting that their sample size is still too small to draw definitive conclusions, but their initial results suggest that there may be an intriguing difference between the Bedey and other Bangladeshi people who are regularly exposed to foamy viruses.

“These are the first humans that are known to be bitten and have introduction of monkey saliva who are not infected at some level,” Linial said.

The researchers hope to test more Bedey people for foamy virus and ask why this group of people may not get infected, although right now the research is on pause due to lack of funding, Linial said. She and Jones-Engel are preparing a grant to submit to the National Institutes of Health this fall to support the continued work.

If their results bear up in more Bedey people, there are a few possible explanations for that apparent difference, Linial said. One is that since the nomads are exposed to infected macaques from a young age, they may mount a lasting immune response to foamy virus as children that adults can’t recreate. Alternatively, these performers may carry genetic differences that confer a natural, heritable resistance to the virus.

Understanding those genetic or environmental factors would give the researchers clues about how all humans respond to foamy virus and whether there are mechanisms built into our immune systems that confer resistance — and, perhaps ultimately, lead to a better understanding of other primate zoonotic infections.

“We’re very interested in why this is,” Linial said. “What’s different about the Bedey from the other people in Bangladesh and South Asia?

Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.

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