VIDO researchers building pandemic preparedness tool kit with the help of bats

But bats also hold deeper secrets that can help us better understand and improve our own health. By unlocking the secrets of bat genes, Dr. Arinjay Banerjee’s (PhD'18) lab at the University of Saskatchewan’s (USask) Vaccine and Infectious Disease Organization (VIDO) is learning how to tackle emerging viruses and help safeguard against disease outbreaks.

“Zoonotic viruses that jump from wildlife into other mammals pose health risks for both humans and livestock species. Learning how reservoir hosts like bats maintain a benign relationship with their viruses not only enables us to better understand the world around us but also empowers us to learn from nature to develop powerful next generation therapies,” said Banerjee.

Banerjee and his trainees have recently published three new papers in academic journals that act as a pandemic preparedness tool kit—a body of foundational data and research that can help shape policy, better understand the immune system of mammals, and even develop prospective therapeutics that could treat diseases.

The Nipah virus is a bat-borne virus that caused outbreaks of disease across Southeast and South Asia for over two decades, with seasonal outbreaks hitting Bangladesh and India every year. With high mortality rates and no licensed treatment or vaccine, Nipah is a large public health concern.

In a recent paper published in Nature Microbiology, Banerjee, USask post-doctoral fellow Dr. Kaushal Baid (PhD), and international colleagues proposed a One Health approach to understanding and responding to the virus.

“Preventing the transmission of Nipah virus is pretty complex because there are several avenues that people can come in contact with it,” said Banerjee. “Bats can transmit it to other animals like pigs, which can then infect humans working with those pigs. People can also become sick from drinking contaminated date palm sap, and we have seen people becoming sick after being in contact with symptomatic individuals in hospital settings.”

Nipah is seen as a model pathogen that can help shape pandemic preparedness efforts. The lessons learned from the Nipah virus outbreaks can be applied to other emerging diseases, particularly the need for increased surveillance that can sound off early warning signals to the global community.

“In our paper we identified that an integrated One Health surveillance strategy is necessary to track the spread of Nipah virus among humans and animals,” said Baid. “This includes the regular screening of high-risk populations and case reporting for those who become sick, testing bats, pigs and other animals in outbreak areas for viral antibodies and the use of this data to develop predictive models and identify future hotspots.”

Understanding how zoonotic viruses survive inside their hosts like bats is a crucial part of any pandemic preparedness puzzle, but it’s a challenging one to solve. In Banerjee’s lab, Baid is also looking to better understand how coronaviruses like SARS-CoV-2 interact with their bat hosts.

“We know that in humans the pro-inflammatory processes go haywire in severe COVID-19 cases,” said Baid. “We’ve been able to demonstrate that some bats mount an early antiviral response to SARS-CoV-2 that is more measured, which may explain their ability to tolerate but not eliminate the infection.”

In a paper published in Cell Reports, Baid found that North America’s big brown bat has an interesting response to SARS-CoV-2.

“We found that these bat cells could rapidly select for a variant with a mutation to the spike protein. This protein plays a key role in some of the more severe COVID-19 cases with poorer disease outcomes,” said Baid.

Baid found that in the bat cells, the virus with a mutation to its spike protein tends to be the one that replicates more. Baid speculates that there is pressure from the bat host that leads to this type of virus being dominant.

“We are speculating that, since the spike protein invokes a strong immune response and plays a role in pathology, bats have specific defences to limit those. This was the first time we were able to show this kind of virus interaction and host responses in these bats,” said Baid.

Baid’s study emphasizes the innate immune response that allows for early control of the virus and limit pathology, which reduces the chance of the bat getting sick from the infection. This is a step to identifying what is behind a bat’s virus tolerance.

“I hope we can try and start translating some of the knowledge we acquire from these species to see if this can be used to develop treatments for humans. It’s very early but there is hope we can take what we learn through this research and translate it into potential therapies in the future,” said Baid.

In a third paper, published in Nature Communications, PhD student Victoria Gonzalez from Banerjee’s lab took a deeper dive into these immune responses, particularly the interferon response pathways, which are series of cell signals that trigger an immune response in two very different bat species—the big brown bat and the black flying fox.

“In humans and other mammals, the interferon response is known to be our first line of defence against viruses,” said Gonzalez. “In this study we took two divergent bat species to evaluate their immune response and then looked to see how that compares to humans.”

Gonzalez found that important antiviral genes were switched on in bats and humans. The bats, however, needed less to protect them from disease.

“In bats a little goes a long way, while a larger response needs to be mounted in humans,” said Gonzalez.

The research also looked closely at the antiviral GBP1 protein, which is very similar in both bats and humans. Despite these similarities, Gonzalez identified a new region in the brown bat’s GBP1 protein that functions differently from humans. When she turned this region off in the big brown bat, the antiviral activity for a specific virus, a bat poxvirus, was completely gone, meaning this region was key for protection.

“It’s nice in the sense that we’re seeing this co-evolution of viruses with their hosts and knowing that there are antiviral genes similar to what we have in humans. It’s kind of paving a way forward to potentially developing therapeutics,” said Gonzalez.

The work in Banerjee’s lab continues, with more discoveries waiting for the team as they dig further into the immune systems of bats and start to tease out more details that can be used to help protect against the next global pandemic and in vaccine and therapy  development around the world.

“We hope to use basic research on zoonotic viruses and their reservoirs hosts to inform the development of powerful next generation therapies and therapeutic targets for humans within the next decade in my laboratory,” said Banerjee.

Article originally published at https://news.usask.ca