Zoonotic diseases: Why are infections from animals so dangerous to hu

In the wake of the COVID-19 global pandemic, which started when the virus SARS-CoV-2 jumped from animals into humans, we ask an important question — why are infections acquired from animals so dangerous to human health?

While it is not yet clear which animals were the source of the new coronavirus — was it bats? Was it pangolins? Was it both? — scientists are sure that SARS-CoV-2, the virus that causes COVID-19, originated from animals.

The numbers of confirmed COVID-19 cases across the world are staggering. According to Johns Hopkins University, more than 730,000 people have contracted the virus and 34,000 people have died.

But zoonotic diseases — that is, diseases acquired from animals — were affecting vast numbers of people across the world before COVID-19 took center stage.

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An international report from 2012, for example, informed that a total of 56 such diseases were responsible for 2.5 billion cases of illness and 2.7 million deaths across the globe each year. These illnesses included rabies, toxoplasmosis, Q fever, Dengue fever, avian influenza, Ebola, and anthrax.

Furthermore, respiratory, flu-like diseases acquired from animals wreaked havoc in the past century. The Spanish flu caused 50 million deaths in 1918, and the Hong Kong flu caused 700,000 deaths in 1968.

So, why are diseases that humans acquire from animals so dangerous? Part of it is due to our immune system. Part of it is natural selection. The specific animal that transmits the virus may also play a role.

Below, we explore some of these factors and how they intertwine.

Animal virus vs. the human immune system

One reason viruses from animals are so dangerous to humans is that people have no means to deal with them. Our immune system was never ‘introduced’ to these novel viruses, so it doesn’t know how to respond to the uninvited guest.

Researchers explain that most of the viruses that enter the human body are successfully destroyed by the immune system or pass through our gastrointestinal system. However, now and then, an animal virus manages to replicate within a human host.

The moment where the animal virus replicates within the body of the first human is crucial. At this critical point, the virus can mutate and evolve “under the selective constraints of the human body for the first time, adapting and improving itself for replication in this new host.”

As this occurs, the human immune system must retaliate. It needs to ‘catch up’ with the virus’ evolution and create an immune response. The human body has never been confronted with this threat before, and therefore, has no pre-existing immunity in its arsenal — so it must devise one fast.

But, this defense — part of the adaptive immune system — takes days or longer to activate. In the meantime, the virus may have already evolved to replicate faster or even escape the immune system’s retaliation.

An ‘evolutionary arms race’

In other words, the animal virus and the human immune system have entered an ‘arms race’ — and like with any arms race, one of the two competitors could win, or both competitors could reach a stalemate.

Medical News Today spoke to Christopher Coleman, assistant professor of Infection Immunology at the University of Nottingham in the United Kingdom, about animal viruses, human hosts, and the role of evolution and natural selection.

“[T]he general assumption,” he explained, “is that as viruses evolve to a host, they become less dangerous to that host (they want to ensure their own transmission so don’t want to rapidly kill the host before they get a chance [to replicate]).”

“This is by no means [always] true, but a virus that adapts to humans might be less dangerous in the long term because the ‘evolutionary arms race’ between virus and host has reached a sort of stalemate where neither is perfectly happy, but neither is killed off.”

– Christopher Coleman

Furthermore, a “virus that fully adapts to an animal host may be completely harmless to humans,” Coleman continued.

The scientist — whose main research focuses on ‘highly pathogenic human coronaviruses’ — gave examples of aggressive animal viruses within the coronavirus family. These include the “‘infectious bronchitis virus’ of chickens, ‘feline infectious peritonitis virus’ in cats, or ‘transmissible gastroenteritis virus,’ which is near 100% fatal in piglets.”

“None of these [viruses] are known to infect or cause any disease in humans,” Coleman said.

“On the other hand, a virus that evolves in animals but also has an ability to infect humans may be more deadly if and or when it infects humans.”

This may be especially true when the animals’ immune systems are very different from those of humans, or when the animals have special defense mechanisms that humans lack.

Bats and their ‘hyper-vigilant’ immunity

For instance, the fact that very harmful viruses such as SARS, MERS, and Ebola have all originated in bats begs the question — what do bats have that we don’t?

How can bats fly around carrying viruses that, in some cases, are extremely deadly to humans (such as Ebola), but that do not seem to harm these creatures in the slightest?

A new study, led by Cara Brook, a postdoctoral Miller Fellow at the University of California Berkeley, asked this very question. The research shows how bats’ unique immune capabilities enable them to carry and maintain a high viral load without getting sick themselves.

“[S]ome bats,” explain Brook and colleagues in their paper, “have an antiviral immune response called the interferon pathway perpetually switched on.”

“In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm.”

— Cara Brook et al

From strength to strength

This is all great news for bats, but what does it do for other mammals? Sadly, not much. The fact that bats have such good defenses means that the virus has all the encouragement it needs to replicate more quickly.

The bats’ unique immune capabilities eventually make the viruses stronger. It is like training with an outstanding competitor and getting stronger as a result.

Brook and her team carried out experiments using cell lines from two species of bats. The results showed that in “both bat species, the strongest antiviral responses were countered by the virus spreading more quickly from cell to cell.”

“This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures, including humans, are not.”

– Cara Brook et al.

“Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology,” says Brook.

COVID-19: bats, pangolins, or snakes?

In the case of the new coronavirus, multiple theories are circulating about the specific animal that passed on SARS-CoV-2 to humans. Scientists have implicated pangolins or even snakes as possible carriers.

Pinning down specific mammals is vital because the animal can offer insights into the genetic structure of the virus and ways to tackle it. However, it is essential not to discount the possibility that the new coronavirus might have several animal sources.

Commenting on the theory that humans contracted SARS-CoV-2 from pangolins, Coleman said: “It’s as good a theory as any […] This, of course, does not mean that pangolins are the only source — it may be that there are other species.”

“For example, with ‘the original’ SARS-CoV, civet cats were the most famous species involved, but there were other small mammals infected. Also, although dromedary camels are the source of MERS-CoV, there is strong evidence that ‘other camelids’ can also be infected.”

Regardless of which animals specifically gave humans the new coronavirus, it may be more important to ask, when and where did the virus mutate?

Two alternative scenarios for COVID-19

In a recent study, researchers led by Kristian Andersen, Ph.D., an associate professor of immunology and microbiology at the Scripps Research Institute in LaJolla, CA, used the available genomic data to determine whether the origin of the new coronavirus was natural or made by humans.

Having determined that the virus is the result of natural evolution, the authors explain that depending on whether the virus adapted in its current form in animals or humans, the course of the new coronavirus pandemic could be quite different.

“[I]f SARS-CoV-2 pre-adapted in another animal species,” write the authors in the journal Nature, “then there is the risk of future re-emergence events.”

In other words, if the virus evolved to its current state in animals, then animals would continue to pass it amongst each other, and the virus could jump back into humans at any point.

Furthermore, the researchers suggest that this scenario would explain why the virus spread so quickly. Seeing that it had already developed its pathogenic traits in animals, SARS-CoV-2 was already ‘trained’ to spread and replicate quickly once it entered its first human host.

“In contrast,” write Andersen and colleagues, “if the adaptive process occurred in humans, then even if repeated [animal-to-human] transfers occur, they are unlikely to take off without the same series of mutations,” therefore minimizing the chances of another outbreak.

For now, it is impossible to know which of the two scenarios is more likely. Only time, and more research, will tell.

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