Why so many coronaviruses from bats?

by Janice Nigro

Nature can still surprise us. One sperm, one egg and you are a whale shark, a red hairy shrimp, or a bat terrorizing humans by showering pandemic disease causing viruses down upon them.

I’m as caught up as everyone else in the interruption of life, business and the stock market brought upon us through the viral disease capturing our full screen attention, novel coronavirus-2019 (COVID-2019). An infectious agent that isn’t even alive. A mere strand of genetic material bundled up and served to us in a few proteins decorated with carbohydrates.

The corona in coronavirus comes from nothing more than its appearance. The viral proteins key for interacting with the target cell are arranged on the surface of the virus like the rays of light beaming from our very own sun, if you were to draw a sun as I do.

The virus enters cells, commandeering eukaryotic resources and the protein translation machinery to reproduce itself. It does this through the recognition of a specific population of cells in the lung that have the receptor for the virus and might already be primed for replication of it.

The identification of the infectious agent and its genome all occurred in an impressive whirlwind timeframe of just a few weeks, from the first clinical observation in December 2019 of a cluster of patients with respiratory symptoms, all connected to a local seafood market in Wuhan, Hubei province, to publication in February 2020.

The precedent of Severe Acute Respiratory Syndrome (SARS), the coronavirus in 2002-2003 that killed ~10% of the people infected, gave investigators a clue as to what they might be looking for. In fact, scientists predicted such a possible imminent crisis in a study of coronaviruses in January of 2019, almost a full year before the current pandemic.

The genome of coronaviruses, the map of their genes, is made up of RNA rather than the DNA that is the building block of our own chromosomes. COVID-2019 has a large genome for an RNA virus at close to 30,000 nucleotides long, which is the length of a small human gene. But to sequence it with today’s technology is a trivial exercise.

Both COVID-2019 and SARS latch onto the lung cells they take over through the same protein receptor, angiotensin I converting enzyme 2 (ACE2). There are just a couple of differences between the point on the two viruses linking them to human cells, which might explain the decreased mortality of COVID-2019 relative to SARS.

Now the story gets a little creepy. The RNA in COVID-2019 looks a lot like a coronavirus sequence in the only mammals known to fly, bats. The sequence of COVID-2019 is ~ 96% similar to this coronavirus sequence and nearly 80% similar to SARS, which is thought to have originated in bats.

The puzzle I wondered about is why bats? COVID-2019 is at least the third coronavirus in less than 20 years to cause a frightening outbreak in humans while others have driven pandemics in livestock. They all seem to have been born in bats.

The lifestyle of bats provides one answer. They tend to live under cozy conditions, in close proximity to each other. Not unlike those of us living in big cities around the world. This proximity gives them the ability to pass pathogens back and forth which may have two consequences: to prevent viruses from going extinct and to create new ones.

Viruses, RNA viruses in particular, are sloppy at copying their genomes and thus generate changes in them at a high rate. They may even recombine with other RNAs, picking up odd bits of genes that may belong to their cellular host to become something new. Like a cancer cell, many of these changes, or mutations, might lead to dead-ends, but once in a while a change improves infection enabling it to jump to an organism other than its own kind.

Voilà, this flying rodent is now the source of our fear and quarantine just as in a cult B-movie horror film. Their viruses infect not only humans but also livestock and chickens. They have even turned up in a deceased beluga whale. So they spread their spawn far and wide.

A little deeper thinking on “why bats?” might make you wonder how they live in a sort of harmony with the production of these viruses which cause pandemic upheaval in the lives of humans or our livestock. Bats live, in fact they thrive for 20 and up to 40 years, while polluting the air, the environment with their viruses. In short, they don’t knock themselves out with their own artillery.

Answering this question, believe it or not, came from scientists looking into the consequences of this mammal’s unique ability to fly.

Flying is a high energy requiring activity producing waste at the cellular level which damages the genomic DNA in the nucleus. This DNA gets released into the cytoplasm, where it really shouldn’t be.

DNA in the cytoplasm is one of the signals used by mammalian cells to identify invading pathogens-yes, even viruses-which trigger the immune system. So if genomic DNA, damaged through the activity of flight, leaks out of the nucleus, it might trick the immune system, causing a state of constant immune activity. In humans, over-activation of the immune response underlies autoimmune diseases which have numerous effects on health, quality of life and aging.

So to fly and to survive, bats must overcome this problem. They do scientists believe, because of a dialed down sensitivity in their immune response to DNA in the cell cytoplasm. The mechanism turning on the factors (interferon) necessary to ramp up the immune response is handicapped.

Infection by viruses, even RNA viruses, can also cause DNA to leak from the nucleus. This diminished immune response in bats to DNA in the cytoplasm is an opportunity for viral replication to take place. If produced at sufficient levels, the virus can go on to infect another organism without destroying the bat.

Producing pandemic inducing viruses might be a fluke, a nifty perk of the evolution of the bat’s ability to fly.

Although the original COVID-2019 patients had direct contact with the same local seafood market, whether the route to transmission between humans includes another animal intermediate is not yet known. Another human transmissible coronavirus, Middle East Respiratory Syndrome (MERS), likely originated in bats but it reached humans via camels. Samples from an infected person and his camel producing the same MERS in genomic sequencing confirmed this mode of transmission. Himalayan palm civets, raccoon dogs, and ferret badgers were possible jumping points for SARS from wild animals to humans.

The in-between animal may be more susceptible than humans for any number of reasons, or perhaps just because it’s in contact with the bats. This animal importantly serves as another incubator extending the time for viral replication and for making mistakes in the viral genome necessary for human infection.

In some manner, through handling or eating, the transfer occurs between an infected animal in proximity to humans, such as the workers in the Wuhan market. COVID-2019 might have been percolating for a while in humans in contact with wild animals at the market until the right combination of RNA changes enabled it to go from one human to another. This is the possible juncture we now face.

The COVID-2019 pandemic has given me a new perspective on our hygienic and purchasing habits, at least here in California. And well, on the idea of the eating and selling of wild animals. I might have once thought it romantic or adventurous or brave to taste bat in a coconut curry prepared by an Indonesian dive guide on a beautiful island not recognized by Google maps. Since the explosion of coronaviruses into my consciousness, I think I might pass the next time I’m offered that dish, no matter who the chef is. Heck, I might even just stop eating meat.

The pandemic does bring up a problem I have already considered when I’m traveling to rural areas of the world I’ve never been to. Should I even be doing it?

In no time, tradition and the Jet Age have clashed, destroying life as we know it. Once this pandemic passes, life might not go back to the way it was. I wonder, could I ever be a vehicle for such opportunistic pathogens that are new to me, to my world? Or am I already a vehicle bringing deadly pathogens to the people and animals living there? This is the concern for some, that a possible increase in the frequency of such pandemics is inevitable based on our expanding human population and our encroachment upon the very environments and animals we are so enamored to see.

Yes, thoughts to ponder while you’re asking yourself about the perks of being a flying mammal.

 

©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.