Renowned and feared as carriers and transmitters – but not sufferers – of deadly viruses like Ebola, Hendra and SARS, bats have been revealed by Burnet Institute research to possess the largest and most diverse range of anti-viral genes in the mammalian world.
The Burnet study by Dr Joshua Hayward and led by Professor Gilda Tachedjian, is an important step towards explaining how and why bats can harbour viruses deadly to most other species of mammal, without falling ill or showing any symptoms.
“It’s been hypothesised there’s something different about the way bats respond to infection, and for decades scientists have been trying to work out what that is,” Dr Hayward said.
“We were looking for a difference that might exist in genes that produce proteins called ‘restriction factors’ that have a direct impact on viral replication, and we found that bats had a much more diverse repertoire of genes for a type of restriction factor called APOBEC3, which are really important for combating retroviruses.”
Published in the journal Molecular Biology and Evolution, the research suggests that bats have found a way to coexist with certain viruses by striking an evolutionary truce in the otherwise relentless battle between virus and host to attack, defend, and adapt.
Rather than kill the virus, bats appear to use their armoury of genes to stop the virus from replicating to levels that would be harmful, which obviates the need for the virus to constantly look for ways to counter the host’s immune response.
Previously, humans were understood to have more APOBEC3 genes than any other mammal, but Dr Hayward found greater numbers in bats, including a sub-type that’s unique.
“What’s interesting about bats is that even though they’ve got these viruses like Ebola and Hendra, they don’t completely suppress them – they can be productively infected, and that’s what allows them to transmit these viruses to humans,” he said.
“So it might not be a matter of completely allowing viral replication or completely crushing it, but regulating it so the bats don’t get sick, so the viruses no longer have an evolutionary selective driving force to come up with more countermeasures to the hosts’ immune response.”
Dr Hayward said the Burnet research is significant for casting new light on what’s already known about the innate immune or ‘interferon’ response, part of the body’s alarm system for infection.
In humans and other mammals, interferon is activated only when a new infection is detected, but in bats the response is switched on permanently.
“To the best of our knowledge, this is the first study that looks at any bat restriction factors, and it’s showing that there’s a significant difference in the gene repertoire for responses to viruses,” Dr Hayward said.
“You combine that with research that shows the anti-viral response is always on, this interferon response, and it basically means that these genes are ready to go all the time in bats.
“One of the most important stages when you get a viral infection is how you respond to it in the very first instance when the virus gets into your cells and starts replicating.
“If these genes are always on, that could go a long way to explaining why bats can get infected, but manage to maintain low numbers of viruses and stop them from getting out of control.”
Dr Hayward said preparations are underway on the next step to test the APOBEC3 genes for their antiviral effects on viruses found in bats, and broader complementary research to test the bats’ battery of genes against known countermeasures to APOBEC3, including Vif, a protein found in HIV.
“Ultimately, improving our understanding of why bats are a significant source of viruses that transmit to humans will help us deal with that problem,” Dr Hayward said.
Bats are known to host more than 60 viruses that can infect humans, and new viruses transmitted by bats are being discovered, including one that killed 24,000 piglets in China’s Guangdong Province in 2016-17.
Identifying these new viruses in animals and quickly determining their potential to infect people is a key way to reduce global health threats.
This study is a collaboration between Burnet Institute, CSIRO’s Health and Biosecurity Unit at the Australian Animal Health Laboratory, Wuhan Institute of Virology, Howard Hughes Medical Institute, University of Minnesota, and Duke-NUS Medical School.
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