A viral pandemic shows us how much we still have to learn, and where we might learn it
I don’t need to remind anyone of the ongoing global pandemic. It’s there. Something you may have heard is that such pandemics become increasingly likely with our spread into the far reaches of the planet and our increases in interactions with more and more animals, be it for agricultural or scientific purposes. Despite the severity of the pandemic, this pattern seems to me unlikely to change. So, we can probably expect further pandemic events in our lifetime, whether or not they have the severity of our current one. One thing we can do to be more prepared for that time, whenever it comes, is to spend more time researching bats.
Bats have a lot going for them. They are the only mammals that fly, they are a keystone species around which many ecosystems depend, and they might be vampires in disguise!* But most importantly and interestingly to human research right now is the unique immune capabilities of bats. Bats host more zoonotic pathogens than any other mammal. A zoonotic pathogen is a pathogen (disease, whether bacterial or viral) that transfers from an animal to a human. And bats have loads of them. Which begs the question: why aren’t bats just falling from the sky all the time? Because bats are tough. Bats are known as viral reservoirs. This means they are able to carry viral loads without ever suffering symptoms. And they’re viral reservoirs for a lot of viruses: SARS, Ebola, Hendra virus, rabies, and, yes, COVID-19 (and the list goes on). Which begs another question: how is this possible?
Something important to realise is that there are lots of bats. As in, lots of species of bats. At 1423 species, bats account for over 20% of all known mammalian species. As mammals, bats share a (relatively) recent evolutionary history with us (our last common ancestor is estimated to have lived around 97 million years ago, give or take, placing it in the Cenomanian period of the upper Cretaceous period and looking like a small rodent). In the time since humans and bats diverged in the tree of life, a lot has happened in their genomes in terms of immune response which has not happened in ours. The bat genome and cellular structures are uniquely equipped to deal with viral infections, and this is for two predominant reasons: firstly, a superior immune response which nullifies viral activity, and secondly, a superior toleration of viral load which prevents inflammation, which is so often the damaging factor in human viruses.
Immune responses
I could sugar-coat this with scientific terms and names of proteins and processes, but the point is very simple: bat immune systems are just better. Humans express proteins known as interferons in response to viral infections, which in turn stimulate other genes which deal with the viral infection. Many of these secondary immune response genes are expressed in bats before they’re even stimulated by interferons. To put it simply: when humans get a virus, the alarm system sounds and the police are on their way. In bats, the police are already in the kitchen making tea. What’s more, bats have more antiviral genes induced by interferons than other mammals. Bats are also better at autophagy, the clearing of damaged cells. They also have high levels of heat shock proteins, which receive viruses, control inflammation, stop cell death, and are even believed to slow the ageing process. Bottom line is simple: you might have a tough immune system, but a bat’s is just better.
Immune tolerance
This is a case of less is better. Humans, and most mammals, have a series of signalling proteins known as the inflammasome which sound a red alert when viruses or other harmful microbes are detected, which in turn sets of a chain of reactions often culminating in something called pyroptosis. Pyroptosis is a form of programmed cell death which is highly inflammatory. Despite this being part of our intrinsic immune response, pyroptosis is a large part of what generates major and minor symptoms in viral infection, and why so many viruses have common symptoms.
Bats, on the other hand, keep their cool. The expression of some of these inflammasome proteins are dampened, and some have evolved out of bats completely. In practice, this leads to no pyroptosis, and the bats live asymptomatically to fly another day.
The end
Studying bats promises to be incredibly fruitful as we try to target harmful inflammatory responses in humans, the overactivation of which leads to diseases including autoimmune and neurogenerative diseases, such as Alzheimer’s. This will take some time, as bats are not yet model organisms for research so the development of a bat research discourse will take some time, but the upside of growing this body of research is obvious, especially in light of the most widespread pandemic of our lifetimes, and in an age where our interactions with the environment suggest that such zoonotic pathogens will only become more and more common in the coming years.
*Or they might not be, we’ll probably never know
Reference article: https://www.nature.com/articles/s41586-020-03128-0
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