Project to prevent bat-borne diseases receives $10 million funding

A young female Little Red Flying Fox at Baldwin Swamp Environment Park in Queensland, Australia. A new grant will allow an international team of researchers to study bat-borne viruses that have recently made the jump to humans. Credit: Mel Christi [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]

In an effort to prevent the spread of some of the world's most lethal diseases, an international research team spanning five continents and including Penn State scientists will study bats in Australia, Bangladesh, Madagascar, and Ghana.

The goal of the work is to unravel the complex dynamics of bat-borne viruses that have recently made the jump to humans, causing concern among global health officials. The Penn State team, led by co-principle investigator, Nita Bharti, assistant professor of biology, will focus on environmental drivers of where bats live, where humans live, and virus transmission risk. Peter Hudson, Willaman Professor of Biology at Penn State is a project co-director.

The international team is led by Raina Plowright, assistant professor in the Department of Microbiology and Immunology at Montana State University (MSU) and is supported by a $10 million cooperative agreement with the Defense Advanced Research Projects Agency, or DARPA, an independent agency of the U.S. Defense Department that funds ambitious and potentially groundbreaking projects.

“Understanding the underlying mechanisms that give rise to virus spillover from bats into domestic animals and humans is a critical step forward in global health today,” said Bharti. “Spillover events have been increasing in frequency and global distribution every year. But science has been a step behind the pathogens and we’ve tended to focus on documenting spillover events and mitigating outbreaks after they happen. In an effort to get ahead of them, our project aims to decipher the ecological processes and molecular interactions that create spillovers and cause outbreaks.”

Collectively called henipaviruses, these bat-borne pathogens were first identified in 1994 after an Australian outbreak of Hendra virus killed a dozen horses and their owner. Outbreaks of a related virus, called Nipah, have since resulted in hundreds of deaths in Malaysia, Bangladesh and India.

"This research brings together one of the biggest teams in the world working on emerging bat pathogens," said Plowright, adding that the project will study how the viruses are transmitted at the cellular level as well as on the scale of whole landscapes. "Ultimately, what we’re trying to do is find new solutions that can prevent people from getting sick.”

What most worries health experts, according to Plowright, is the potential for henipaviruses to cause future pandemics if human-to-human transmissions increase or new henipaviruses emerge that are more transmissible among humans. The diseases are highly lethal—up to three-quarters of infected individuals die—and there is no cure or vaccine for human infections.

According to Hudson, insights into how and why henipaviruses jump to humans could also help prevent outbreaks of other bat-borne diseases such as SARS and Ebola, which killed over 11,000 people in West Africa from 2014 to 2016. A 2018 outbreak of Nipah virus in India caused 17 human fatalities. These repeated viral spillovers and subsequent outbreaks demonstrate that scientists haven't fully understood the human-bat interactions at the root cause of the problem.

"I think we're on the edge of finding out," said Hudson.

Ecological changes, such as deforestation, likely play a significant role in causing henipavirus outbreaks. The team found that loss of native forests leads to insufficient nutritional resources for the bats, driving them into areas that are occupied by humans and domestic animals. This displacement occurs during periods of nutritional stress, which are thought to suppress the bats' immune systems and cause the animals to excrete viruses in urine and other body fluids. Urban and agricultural areas can simultaneously provide lower quality substitute foods for the bats, as well as inadvertent proximity to new hosts for their viruses.

However, the flying mammals are not inherently a threat to global health. They play an important role in tree pollination and in promoting ecosystem health. Bats have likely survived with these viruses for a very long time and only recently caused illness in humans. The team believes that land pressure and habitat encroachment, two globally pervasive problems, have played important roles in viral spillover.

“Henipaviruses are also found in bats across Africa and Asia, and we don't know how many are spilling over into other animals and people in places with poor surveillance," said Plowright.

Biological samples taken from the bats across the team’s global study locations will be sent to Rocky Mountain Labs, the U.S. National Institutes of Health facility in Hamilton, Montana, which is specially equipped to study emerging pathogens. Researchers there will inventory the viruses, document their genetic makeup, and use controlled cell culture experiments to assess their ability to infect humans.

Meanwhile, Bharti’s team will be integrating long-term weather data, field observations, and satellite imagery to track environmental variables such as changes in weather and climate, forest cover and species composition, and human habitat.

Analyzing long-term weather data throughout eastern Australia, where viral spillover from bats has occurred, will help Bharti identify environmental factors that may be impacting the ecosystem, particularly the trees that provide nutrition for the bats and the bats themselves. Bharti’s team will also quantify the past several decades of changes in forest cover, specifically the loss of four critical species that provide bat nutrition during the lean winter season, to estimate deficits in food resources for the shrinking bat populations. Finally, Bharti’s team will measure changes in land use and human population distribution to better understand the dynamics of human-bat interactions. This will also identify areas at high risk for human-bat interactions and viral spillover so the team can inform targeted, preventative measures and rapid response protocols.

Overall, the team will study short- and long-term ecosystem dynamics to measure changing contact between bats and humans as well as nutritional stress and the animals' immune response to nutritional stress.

By putting together all of those pieces, the research team will develop mathematical models that predict outbreaks based on the presence of henipaviruses and environmental conditions that stress bat populations. That would give health officials information that could help them prepare for, or even prevent, future outbreaks.

One solution to these deadly diseases may be simpler than once thought: protecting bat habitat or even restoring native food sources such as flowering trees in areas away from people. Bharti leads the team that is using multispectral satellite imagery and trends in climate data to determine where critical tree species were lost, where they remain and should be protected, and where they should be replanted. The team must optimize these locations for the greatest odds of tree survival, a high likelihood of bat utilization, and the lowest risk of viral spillover.

The research team also includes scientists from Johns Hopkins, Cornell, Cambridge, UCLA, Rocky Mountain Laboratories in Montana, Griffith University in Australia and five other universities and institutions.

CONTACT

Nita Bharti: nita@psu.edu

Sam Sholtis: samsholtis@psu.edu, 814-865-1930