While the importance of monitoring emerging variants in human populations is top of mind for many, there is also a need to monitor mutations in animal populations, says Arinjay Banerjee, research scientist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization and head of a research group that studies zoonotic viruses and comparative immunology.
The increased movement of human populations, climate change, deforestation and our increased contact with wild and domestic animals, as well as livestock, all play a role in the emergence of new zoonotic diseases. Rabies, salmonella, the West Nile virus, Ebola, and Lyme disease are just a few of the many examples of common diseases that humans can become infected with as a result of exposure to infected animals.
Much of Banerjee’s work involves understanding viral transmission in different animal populations, the possibility for human-to-animal transmission and subsequent reinfection of humans from animal reservoirs. Banerjee says that governments are going to need to fund surveillance of animal populations that can become infected with the SARS-CoV-2 virus. This will become more important in understanding the movement of the virus from non-human hosts back to humans – and the concern that raises for potentially dangerous viral mutations.
Outbreaks in minks have been reported around the world, including one in B.C. that resulted in minks re-infecting farmers. The virus also has been shown to infect populations of a very common species of white-tailed deer in North America.
“Different variants are differentially susceptible to neutralization by some of these vaccines, and laboratory data is starting to show why … and what they mean,” says Banerjee. “But what they don’t know is if these viruses can change in animals when they infect alternate animals. And if the viruses were to change, what are the repercussions of that on humans that are now immune, partially protected or fully protected?
“Whether (those future animal mutations) are going to be more pathogenic, less pathogenic – we just don’t know.”
Banerjee and his team have worked on research proposing to identify a list of animals that are at high risk of infection based on the similarities in the animals’ ACE-2 receptors to those of humans. The angiotensin-converting enzyme 2, or ACE2 “receptor,” is a protein that provides the entry point for the coronavirus to hook into and infect a wide range of human cells.
“There’s just lots of animals and lots of wildlife. How do you prioritize? Where does the money come from? There’s a lot of economical questions that have to be addressed before you can just attempt to survey a huge number of animals,” he says.
Bats aren’t all bad news
When it comes to the many unknowns of COVID-19, animal populations needn’t solely be a source of anxiety. Banerjee says there is also a lot we can learn from animal viral infections that may teach us how to combat some of the harms of SARS-CoV-2 in humans.
One animal that’s gotten a lot of bad press over the years may hold answers. Bats can live with a multitude of viral infections in part because after more than 50 million years of evolution, their immune systems and the viruses they host have reached a sort of equilibrium in which they are able to coexist.
One theory for how bats are able to coexist with viruses in the absence of disease is that they have evolved a unique immune system that enables them to neutralize incoming RNA viruses without generating a massive proinflammatory response. Proinflammatory responses are designed to regulate growth and the reactions in the immune system that attack pathogens in the body but can also cause adverse impacts on the host in the process, damaging tissue or triggering immunopathology. It’s this inflammatory suppression that might prove to be the most useful for human resilience in the face of SARS-CoV-2.
“We studied the MERS-CoV, the natural cousin of SARS-CoV-2, and we’ve shown that MERS does not induce inflammatory responses in bats,” says Banerjee. “(MERS-CoV) actually can block good antiviral responses in human cells. So, bat cells have a way of evading this blocking mechanism.”
Bats evade the virus’s ability to block antiviral interferon responses. Interferons, as their name suggests, interfere with viral replication in the cells of mammals and promote not only cytokine production but also the natural killer cell functions. Bats have a strict regulation of these pro-inflammatory cytokines, such as TNFalpha. Banerjee says that if we can learn how bats regulate coronavirus infection-mediated regulation of these inflammatory processes, it might allow us to identify novel drug targets or therapeutic molecules for other mammals, such as humans. In the future, this might help us manage the severe and fatal infections that come with these zoonotic coronaviruses.
Although the research is still underway, Banerjee says he is hoping to show whether understanding these inflammatory blockers may be useful in treating patients infected with long COVID. “That’s something that we’re embarking on to test and identify. We’ll let you know in a few months.”