Are coronaviruses bioweapons of bats?

by Janice Nigro

If you had asked me a month ago what I knew about bats, I would have said, “They are the only flying mammals on Earth.” That’s it.

While the world has been spinning out of control in the last two months over the Covid-19 pandemic, I have spent a portion of my seemingly infinite lockdown time trying to understand how it’s possible the only flying mammal could be the source of so much human anguish, for us and our animals. I have a new respect for the small flying mammal. And the process of evolution. Because evolution is what got us here.

Humans don’t fly, not yet, but they do get sick from coronaviruses. Why do bats remain asymptomatic?

What does it mean to be sick with Covid-19?

Viruses, like Covid-19, which are not much more than a package of genetic material, set up shop in a specific cells. Even though they are not living, viruses hack into the cell system, taking over basic activities to make their own copies.

Fever begins when a region of the brain (the hypothalamus) detects molecules in the body common to a variety of foreign pathogens. Some of these basic primitive signals from infectious agents are DNA in the cytoplasm of cells or certain chains of carbohydrates.

Coughing starts when the body tries to expel the virus or accumulating waste from dead cells. Viral replication kills cells directly or because they can no longer perform their normal functions.

The more serious complications ironically arise during the fight initiated by the immune system, the exact cells clearing up the infection. During a less severe disease course, a choreographed dance occurs between the first responder immune cells and the second wave of more sophisticated immune cell types through molecules called chemokines. It is the second wave which brings specific antibodies against the virus or pathogen and provides the memory in our immune system for defense against future infections. Chemokines not only attract cells to the infected site, they also activate them to clear up infections or destroy the pathogen before it can do any harm.

The dance falls into disarray, like traffic in Jakarta, in more complicated cases of the disease. In coronaviruses, such as Covid-19 or Severe Acute Respiratory Syndrome (SARS), an exaggerated release of chemokines occurs leading to a massive influx of activated immune cells. The cells hit uninfected as well as infected cells, and begin to destroy healthy tissue, disrupting normal exchange occurring in the blood vessels in the lungs and causing multi-organ failure.

In one final blow, when the body attempts to repair the lung damage, it does so poorly, impairing breathing to the point of causing death.

In a dramatic twist, the fight to stop the virus is what kills people. This doesn’t happen in bats.

“Flight as Fever” hypothesis
A common symptom of infection is fever, and it is a primary defense mechanism against disease of any type. The increase in temperature energizes the immune system to do its job, which is to clear the body of the virus or other pathogen.

In the “Flight as Fever” hypothesis, flight takes the place of fever in bats. Flight is a high metabolism requiring activity which temporarily raises the animal’s temperature. A higher temperature during flight might be enough to juice up the activity of the immune system to clear the animal of the virus before it has any pathological effect.

The problem with this idea is that bats carry high titers of virus. Infected bats still make virus, but they don’t suffer.

It’s immune tolerance
If the human immune system overreacts to the virus, the opposite appears to happen in infected bats: no reaction. They just pump out virus during an infection.

It’s in the genes! Our own human genomes have developed over time in response to our activities and our environments. Darker skinned people survived better in regions of the world closer to the equator, while lighter skinned people dominate farther away where there is less sun.

In bats, flying might have provided conditions for the selection of differences in biological systems involved in responding to disease. The high metabolic nature of flying produces chemical byproducts that, for one, damage DNA which simulates pathogenic invasion and a trigger for immune response. As a routine activity, flying might mimic conditions creating an autoimmune-like disease state in bats. In humans, autoimmune diseases such as systemic lupus erythematosus, have numerous effects on health, quality of life and aging.

Some of the proteins within cells critical for linking the detection of pathogenic DNA to the immune system are handicapped in bats. Sequencing of entire bat genomes has also shown that genes involved in immune cell function are also skewed toward different functions. For example, bats have an expanded set of genes, relative to humans, for a type of cytokine associated with stimulating a less aggressive immune response.

These discoveries in the genetic data generate a picture that the immune system in bats ignores or tolerates infection unlike in humans or other animals in so-called spillover events.

The genome of bats may have adapted in other ways to tolerate the presence of virus that aren’t yet understood. Some genes in bats might have changed so that they can now block against death induced by viral replication in a way that human or other animal cells cannot.

But is tolerance of the immune system to viral replication just a consequence of flying or is there another reason bats are making viruses? Is the ability to produce virus also a process selected for during their evolution?

Are coronaviruses a bioweapon for bats?
We probably wouldn’t be here today without viruses, as they do have a part in propelling evolution forward over time. But pumping out virus may have a practical purpose for bats in the here and now: biological warfare.

The bats that produce virus might have one more weapon to lob against predators. Viruses that infect and kill predators may help to maintain populations of bats, which produce only a single pup per year. Any bat back in time with that superpower might have had a survival advantage over other less well-equipped animals.

The bats of today are the product of the evolutionary refinement of some creature from 60 million or more years ago that realized he could take off to escape predators and still reproduce. Byproducts of the finetuning of flying over millions of years are perhaps longer life and the ability to live in equilibrium with viruses. Those that could do all that ended up with viruses as another potential tool in their war chest for survival. Over time, their genomes might have evolved to adapt to this new advantage.

I can’t help but see the parallels of the disease course within the human population. Some people die from the virus while other infected individuals have no symptoms at all. Just like bats. And just like bats, these people are carriers of the disease for an extended period of time.

I guess we just might take more lessons from our flying mammal friends (or foes) to understand the disease course of Covid-19 in different people worldwide and how to treat it.

 

©Janice Marie Nigro/janikiInk.com

Looking for a scientific editor or writer? Contact Janice Nigro at Janice Nigro Ink. I have published in Cell, Science, and Nature, and articles I have edited have appeared in Cancer Research, Clinical Cancer Research, PLoSONE, the Journal of Surgical Oncology, and Oncotarget.