Forwarded messages, reddit memes, chats with histrionic neighbours: ever since we’ve been unwittingly forced into quarantine by the global pandemic, the coronavirus has been all we can talk about. Every great villain has an origin story, and there has been no shortage of interest regarding the source of this “novel” threat.
While there was the initial, Hounds of Baskerville – esque conspiracy flying around about China’s alleged bioweapon scheme gone awry, we quickly shifted to a different theory: one with more proof, but no less room for imagination.
And this is where the bats come in.
Here’s a sunny image: a crowded wet market in a narrow street in China, the overpowering smell of fish in the air, a wilderness of people and animals alike, live animals that some of us have never even heard of (*ahem* pangolins *ahem*) being sold to eat. While this is a foreign and perhaps terrifying picture for some of us, the fact remains that for others, these exotic markets are just considered a cheap and fresh alternative to supermarkets (where you can also buy the aforementioned pangolin or two).
These wet-markets are the alleged birthplace of the CoV-2, though it’s really more of a rebirth.
Initial research indicated that the coronavirus, which causes severe acute respiratory syndrome (fondly known as SARS), was actually a virus found in bats that mutated and crossed over to human hosts. More recently, research has found a greater likelihood that the virus actually shifted, or “spilled over”, from pangolins. Common questions that may arise at this point are: “How did it mutate?”, “Why did it mutate?”, and “Can someone please tell me what a pangolin is?”, etc. In this article, I will attempt to answer (most) of these questions.
Zoonosis – an introduction
A zoonosis is an infectious disease caused by a pathogen (bacteria, viruses, parasites, etc.) that has jumped from non-human animals to humans.
A way of thinking about it is like an infectious (in Covid’s case, viral) “spillover” between species.
Examples of zoonoses include Ebola, Influenza, many strains of bird and swine flu, and more recently, the Coronavirus. In fact, according to the National Institute of Health, zoonoses account for 60% of known infectious diseases and 75% of emerging infectious diseases. Here is a list of some animals and the zoonotic diseases they are associated with:
- Cats: toxoplasmosis, ringworm
- Bats: Ebola virus, SARS, MERS, Nipah virus
- Dogs: rabies, salmonella
- Rodents: plague, salmonellosis
How do these viruses transmit from animals to humans?
There are a number of modes of transmission, including:
- Direct contact: Coming in contact with an animal’s bodily fluids through bites, scratches, petting, etc.
- Indirect contact: Through contaminated areas or surfaces.
- Vector-borne: Being bitten by a mosquito, tick, flea, etc.
- Foodborne: Consuming unsafe food materials like raw fruits or vegetables, uncooked meat, etc. that has been contaminated by an infected animal’s faeces.
- Waterborne: Drinking water that has been contaminated by an infected animal’s faeces.
(Multiple studies indicate that bats and primates are more likely to harbour zoonotic viruses than other taxonomic orders.)
Viral zoonoses: Host Switching, Emergence and Evolution
Now that we’ve covered the (boring) basics, we can begin our attempt at understanding zoonotic transmission from a more virological standpoint.
Zoonotic viruses don’t always become full blown crises like the one we’re dealing with today. Three stages of viral disease emergence leading to successful host-switching can be identified:
(i) Dead-end host spillover (Oops): initial single infection of a new host with no onward transmission
(ii) Outbreaks (Yikes): spillovers that go on to cause local chains of transmission in the new host population before epidemic fade-out
(iii) Epidemic (Very bad news): epidemic or sustained host-to-host disease transmission in the new host population
If there’s one thing evolution has taught us, it’s that there is no genetic perfection. In the genetic sense, striving for perfection is simply adapting and evolving to be most suited to your environment. This is precisely what makes cancer so difficult to cure: it keeps evolving to develop resistance to medication.
It’s no wonder that cross-species transmission of viruses is more common in rapidly evolving viruses. Complex organisms, like humans, are nothing short of biological fortresses, with chemical and mechanical barriers ready to impale “invaders” at every step. In order to infect a new host, a virus must be able to efficiently infect the appropriate cells of the new host. This is far from easy. Apart from mechanical barriers and innate antiviral responses, the potential host cells have the ability to resist infection at multiple stages through a series of cellular processes (such as receptor binding, entry or fusion, trafficking within the cell, gene expression and genome regulation). Basically, the more barriers an organism has in place, the more changes the virus has to go through, and it gets increasingly harder to cross the host range barrier. Furthermore, the production and shedding of infectious viruses may also be host-specific.
While evolutionary changes are not always required for a virus to infect a new host (some viruses have a wider host range than others and are considered “generalist” viruses while others naturally infect only one or two closely related hosts and are called “specialist” viruses), in other cases emergence requires the evolution of the virus to allow efficient infection and transmission within the new host.This is where another basic concept of genetics and evolution comes into play: variation. The greater the level of its genetic variation, the more likely a virus is to adapt to the new host. (A detailed explanation of how viruses infect host cells is a topic for another time).
In fact, a very recent study by the UofGlasgow, published in PNAS, suggests that the risk of zoonotic transmission is likely independent of the animal it comes from, rather it depends on the characteristics of the virus itself.
While we may see the virus as an inconvenience, at best, and a symbol of doom, at worst, one can’t help but appreciate the sheer scale of molecular and evolutionary prowess a virus like the CoV-2 must have to make it in the big leagues. Even on the dark side of biology, it’s the survival of the fittest.
Host plasticity and pandemic potential
Let’s talk about plasticity. Are some viruses more advantaged than others, zoonotically? A paper published in October, 2015 in Nature, details research that used multiple statistical analysis methods to uncover key transmission mechanisms in zoonotic viruses. Key characteristics of pandemic potential that were evaluated for associations with viral traits and high-risk disease transmission interfaces include host plasticity, human-to-human transmissibility and geographic distribution.
(What exactly is host plasticity? It can be simply thought of as the taxonomic range of hosts that a virus is capable of infecting. For example, consider a virus , let’s call it c00L, that can be found in bats (order chiroptera), cats (order carnivora) and monkeys (order primates), and another virus, N00b, that is found to infect rats (order rodentia) and cats (order carnivora). In this case, c00L has higher host plasticity than N00b.)
While the study yielded many enlightening results, perhaps the most interesting was the link that became apparent between the aforementioned key characteristics. The study found that 63% of zoonotic viruses infecting humans were reported in animal hosts from at least two different taxonomic orders and 45% were reported in four or more orders, in addition to humans. Thus, viruses are significantly more likely to be human-to-human transmissible with each increase in virus host plasticity. Similarly, the data showed that viruses were more likely to be in broader geographic range categories with increasing host plasticity.
From: Spillover and pandemic properties of zoonotic viruses with high host plasticity
The Latest: Driving Factors and (Un)surprising Revelations
Our ecosystem is a complex, interlinked dimension. The smallest stone in the pond can cause far-reaching ripples. It should come as no surprise to us, then, that humankind’s (often selfish) interference in nature has had a hand in the increasing threat of zoonosis.
A recent study in the Proceedings of the Royal Society B Journal classified organisms according to their listing in the IUCN Red List, and used this as the basis of the study. This established connections between human activities relating to shifts in mammalian population, and the spread of zoonotic viruses.
- Exploitation: The researchers found that amongst the species listed as threatened, those with a population size reduction owing to exploitation have over twice as many zoonotic viruses as compared to threatened species listed for other reasons. A possible reason for this is that the opportunity for pathogen spillover increases because of the close contact between wildlife and humans involved in activities like hunting and wild animal trade. Threatened species with population reductions owing to declines in occupancy, extent of occurrence and/or habitat quality were also predicted to host nearly twice as many zoonotic viruses compared to threatened species declining for other reasons,
- Domestication: The study found that domesticated species status had the largest influence on the number of mammalian viruses shared with humans with eight times more zoonotic viruses predicted in a given domesticated mammal species compared to wild mammalian species. Both the RSP study and the Nature study also highlighted that domestic animals are at the centre of the unipartite/bipartite viral sharing network among mammalian hosts (a sort of web that helps us visually understand zoonotic transmission across species).
Species that have increased in abundance and even expanded their range despite large-scale anthropogenically driven landscape change and urbanization are more likely to be generalist species that have adapted to human-dominated landscapes. Many species listed as Least Concern with increasing abundance by the IUCN Red List are adaptable wild mammalian species that have benefitted from a close relationship with humans. These species could have habitat and dietary niches that overlap with humans in dwellings or in agricultural practices, further enabling direct and indirect contact with similarly adapted sympatric species, domesticated species and humans.
Conclusion
Zoonosis, being the rising cause of more and more pathogens, is very relevant to learn about and to research. Scientists over the world are trying to understand these viral networks better. With the coronavirus pandemic in full swing, understanding the nature and mechanisms of these viruses has become more urgent than ever.
While I wouldn’t say that my article is “all you need to know”, I have tried to cover the most novel and fascinating aspects of this phenomenon, so that we can begin to understand it in biological, anthropological and medical terms, paying special attention to recent studies and relatively new findings. The importance of finding answers is paramount, and for those of us who aren’t getting our hands dirty in the labs (or getting our hands dirty at all), awareness and information is crucial. Therefore, I’m including a list for further research at the end of this article.
Beyond just understanding, I personally find that in the face of biological crises that tend to distort and terrify, we should never lose appreciation for the evolutionary masterpiece that is the world of pathogens. Microscopic, single-celled, without a developed system; yet spanning over species and continents: relentlessly adapting. A threat like this one, one so complex that we haven’t even completely understood it, operates on the pillars of biology: adaptation, evolution, variation.
Finally, and perhaps, most importantly, zoonosis reminds us that humankind may toy with nature, but in the end, we are trapped in its web – a single network. What goes around will come around. While we may pretend to have distanced ourselves from it, nature’s claim on us is indelible.
We have questions, but everyday we get closer to answers. Though I suppose some questions will always delude us…. Five pages and I still don’t know what a pangolin is.
Further research + Sources:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546865/
- https://www.pnas.org/content/early/2020/04/08/1919176117
- https://royalsocietypublishing.org/doi/full/10.1098/rspb.2019.2736?af=R
- https://www.nature.com/articles/srep14830
- https://edition.cnn.com/2020/03/19/health/coronavirus-human-actions-intl/index.html