By Efstathia Robakis
As the COVID-19* pandemic continues to unfold, scientists are scrambling to answer old questions as new ones continue to arise. Though it doesn’t seem pressing now, given the urgency of so many other real and immediate issues related to the virus’ stranglehold on the world, the question of the virus’ origins is an important one. Understanding where a zoonotic disease — one that spreads from animals to humans — came from can have a big impact on how it’s addressed at every level, including medically, ecologically, and administratively.
The history of spillovers is surely longer than the human effort to document them. While there may be many diseases that cause more deaths, zoonoses can pack a punch; some of the more infamous ones include HIV, ebola, and rabies. Evidence increasingly indicates that COVID-19 most likely (but not certainly) came from a bat reservoir, though the intermediate host between bats and humans, if there is one, is still unknown. A reservoir is an animal that can host and transmit a disease without exhibiting symptoms, and bats appear to host many more zoonoses than other mammals. This means it’s not unreasonable for experts to look into them as reservoirs for COVID-19.
Andy Morffew | CC BY 2.0
A 2017 paper in Nature compared the number of known viruses carried by a variety of domesticated and wild mammals, from mice to armadillos; the authors showed that viral richness (that is, the number of viruses an animal carries, regardless of whether they are transmissible to humans) was highest in bats, primates, and rodents. When the authors further focused on a subset of 188 known zoonotic diseases, they found that — even when accounting for potentially confounding variables, such as how much habitat overlap there is between animal reservoirs and humans — bats hosted a significantly higher number of zoonotic diseases than other mammals. Models from the study indicate that, apart from the overall viral richness of a species, proximity to humans (for example, as a result of increasing urbanization) and phylogenetic closeness to humans were both important factors for predicting zoonoses. But this isn’t the whole story: how are bats carrying all these diseases without falling ill themselves?
A recent study by Cara Brook and colleagues may have shed some much-needed light on the situation at the molecular level. Just like birds, bats need fast metabolisms to fly. However, high metabolic rates can cause cell damage, and are generally associated with shorter lifespans in small mammals: think of short-lived mice versus long-lived elephants. Bats, which easily live to 20 years and older, are a notable exception to this trend. Although researchers are still trying to understand the exact mechanisms underlying the relationship between metabolism and longevity, it appears that bats combat the deteriorative effects of high metabolic rates at least in part by maintaining strong, consistent anti-inflammatory responses at the molecular level. Slowing down inflammation, and therefore inflammation-driven aging, is probably in turn responsible for their long lifespan. In short, reduced inflammation is bats’ strategy for mitigating the deleterious effects of the fast metabolism needed for flight, and it also happens to result in a long life.
According to Brook and colleagues, this unique anti-inflammatory adaptation allows bats tolerate extremely strong antiviral immune responses, and is likely connected to their viral richness and high number of zoonoses. Typically, fighting off a virus causes unpleasant inflammation, as in the fever and pain you may feel when you have the flu. In bats, their already-established anti-inflammatory traits mean that they are also able to mount a powerful anti-virus response without experiencing those other pesky symptoms of inflammation.
The study’s authors used a combination of in vitro studies and computer models to better understand interferon, the molecule in bats that signals their cells are under attack when a virus is detected and stimulates cells’ defenses. As compared to other vertebrates, not only is the production of interferon in bats triggered more easily, but more is also expressed. In most mammals, an interferon response as robust as that of bats would would elicit a great deal of concomitant inflammation; because bats already have a strong anti-inflammatory mechanism in place, they avoid experiencing these negative side effects.
This powerful expression of interferon means that bats’ cells are better protected against viruses than they otherwise would be. To further illustrate this, the authors of the study compared the anti-viral behavior of bat cells to those of an African green monkey, a species which does not produce interferon at all. Where the monkey cells quickly succumbed to their infections, the bat cells persisted, remaining resistant to the viruses. But while the bats’ cells don’t die, neither do the viruses — cells stay alive and harbor a growing number of viruses as they replicate and transfer from cell to cell within the host. The bat may feel fine, but its immune system is inadvertently encouraging the speedy evolution of the virus. When viruses spillover from bats to humans, either directly or through an intermediate host, our immune systems just aren’t prepared to combat them.
USFWS/Ann Froschauer | Public Domain Mark 1.0
Of course, a great deal of research still needs to be done to fully elucidate what’s going on inside bats, but host physiology is only one part of a complex web of factors that results in spillovers from both bats and other animals.
Although zoonoses may be more likely to originate from bats, we also know that spillovers are also strongly affected by environmental and behavioral factors. Perhaps most importantly, we have a great deal of control over many of these factors, whether through conservation efforts, regulation of the bushmeat trade, or urbanization strategies. On a personal level, things like vaccination and good hygiene also go a long way.
Regardless of COVID-19’s origins in particular, it is important that we see bats clearly: not as malicious vectors of disease, but as unique and inherently valuable animals with their own fascinating physiologies, behaviors, and evolutionary histories. Bats are essential to a variety of ecosystems and are integral to plant growth, pest control, and pollination globally. The problem of zoonoses lies not with bats — or with any other animal reservoirs — but in our own interactions with them. As we increasingly alter habitats and ecosystems, the lessons we learn from this pandemic are ones we should be careful to keep in mind well into the future.
* This article refers only to COVID-19 because “coronavirus” - although acceptable for journalistic use in this context - is a general word for a group of viruses with similar morphological and chemical structures. COVID-19 is the disease, while the virus causing it is SARS-COV-2. Read this Vox article for more information on why what we choose to call viruses is important.
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