Origin of the Viruses

This week I was asked to write a blog about viruses and virus-like particles. My professor decided to go easy on me and only wants me to discuss the evolutionary origin theories of viruses and which I think is most likely.

Welp.

Let’s start with a description of what viruses are, and how they are different from other organisms. If you read my last blog,[1] I mentioned that viruses aren’t considered ‘living’ by certain standards because they can’t replicate or produce energy without a cell’s assistance. They are basically a string of RNA or DNA with a protein coat that go around parasitizing cells (animal, plant, bacteria, protozoa, etc.) and reproducing. While some have more “accessories” like proteins that can help them replicate their genome, most lack the complex machinery that even simple cells have for energy production, metabolism, and other life processes. Nothing else on earth seems to look like viruses, so of course in our classification system that likes to group and link things together based on their similarities, viruses are just out there on their own.


https://upload.wikimedia.org/wikipedia/commons/f/f2/Icosahedral_Adenoviruses.jpg

There are three prevalent ideas that have been the main theories for where viruses come from. They are the reduction hypothesis, the escape hypothesis, and the virus-first hypothesis.

The Reduction Hypothesis starts with the presumption that everything started out as primitive cells. During the course of evolution, these cells somehow lost most of their machinery that made them cells, until all that was left was the genome (be it RNA or DNA), a protein coat to protect it, and some elements to help them reproduce that genome once they entered another cell. The fact that there aren’t any organisms that seem to be ‘intermediates’ between cells and viruses seemed to defeat this theory, as it is expected that there would have to be some sort of middle step that the cells went through on their degeneration to viruses. There’s also the question of how cells went from a lipid membrane (the outside-most layer of the cell made up of fatty molecules called lipids) to a protein coat in viruses (the protein capsid that protects the genome). But there is support for this theory in the recently discovered mimivirus and megavirus, both of which are larger than some small bacteria (a very unusual trait, as every other virus discovered up till now was too small to be seen even on a microscope). These viruses also have a very complex genome, and mimivirus in particular has enzymes and proteins that were only expected to be found in true, living cells.[2] Thus, these two viruses can be seen as the necessary intermediate for the reduction hypothesis.

The Escape Hypothesis also starts with cells. The idea is that pieces of cell genome—again, either RNA or DNA—‘escaped’ the primordial cell and decided they wanted to live on their own (figuratively speaking, of course). This theory came from similar genome pieces that we actually see in biology. Plasmids, for example, are small pieces of bacterial DNA that are separate from the cell’s genome. They code for special goodies (like antibiotic resistance) that are not necessary for life, and use their own machinery to replicate those genes. Plasmids are incredibly mobile, and easily passed between bacteria, even bacteria that aren’t related. Thus the idea that something like these could have escaped a bacteria and decided to parasitize the host’s machinery for replication isn’t so far-fetched.[3]

The Virus-first Hypothesis assumes that viruses were the original form, and as cells started to arise, they began to parasitize them and evolve along with them. There are some questions for this theory. If current viruses require cells in order to replicate and survive, what did these ancestral viruses use? If they started out as more primitive than the current viruses, where did they get all the complex components that they have today? If the natural evolutionary process leads to something large and complex like mimiviruses, why are there still small and simple viruses around that didn’t get the memo? There are also supports, however. Early viruses may have found some sort of ‘soup’ of nutrients to grow in, then transitioned to cells once they arose, losing their methods of autonomous replication in the process.[4] There are also, for lack of a better term, biologic components—virus-like particles—that seem to be examples of what these pre-viruses were like. Viroids are the smallest infectious agent known. They are nothing more than a short, circular strand of RNA; no protein coat, no particular complexity, just a little piece of genome floating around infecting cells, like a rogue plasmid. The idea is that these viroids are very similar to what the primordial viruses were like.[5] That still begs the question why so many viroids were completely left behind in the evolutionary journey, but it is unlikely to receive an answer any time soon.

Now on to the second part of the assignment: which theory do I find most likely. It may sound cliché, but I see no reason to choose one to the exclusion of the others. Perhaps there were primitive viroid-like organisms that existed before proper cells developed, then evolved with them to become the viruses we know today. But that explanation doesn’t seem to fit every known virus, such as the mimiviruses which look like intermediates between cells and viruses. Maybe they once were cells, then started to regress until they are now something akin to a virus, but larger and more complex than most any other known. Still other viruses may have arisen from “gene escape events,”[6] like the human hepatitis delta virus which contains coding genes very close to the ones found in human cells.[7]

Science is very limited when it comes to testing things for which we have no current comparison. Using the laws of the present to try and discover the laws of the past can only reveal so much. Thus, the question of the origin of viruses cannot be clearly discovered by what we know now; obviously what happened back then is no longer happening, or at least not in the same way. However, it is still interesting to see the incredible variation among these absurdly simple components, and marvel at how something not even considered to be alive has such a great impact on the world and its inhabitants.


[1] https://vetmedone.health.blog/2019/04/07/how-to-stop-a-virus/

[2] https://www.sciencedirect.com/science/article/pii/S0168170205002376?via%3Dihub

[3] https://mmbr.asm.org/content/74/3/434.long

[4] https://www.sciencedirect.com/science/article/pii/S1879625713001028?via%3Dihub

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609113/

[6] Ibid.

[7] Ibid.

How to Stop a Virus?

Viruses are similar to bacteria in that they are microscopic, disease causing organisms. Unlike bacteria, however, there is a constant debate about whether or not viruses are actually alive. By certain standards, viruses are not living organisms because they depend on a cell to replicate and survive, be it an animal, plant, or bacteria. Nonetheless, viruses are every bit as widespread as bacteria, and some can cause deadly diseases.

For example, Epizootic Hemorrhagic Disease Virus—or EHDV—is a virus that causes severe illness and death in wild ruminant populations, especially white-tailed deer. Within a week of infection, deer will exhibit weakness, drooling and bloody diarrhea. They have a high fever which they try to cool by laying in water, before they suddenly fall unconscious and die.[1] Up to 40% of the deer population can die of this disease.[2]

https://www.realtree.com/sites/default/files/styles/site_large/public/content/inserts/realtree-ehd-deer-misourrideptofconservation.jpg?itok=OASwuiFQ

A type of gnat called Culicoides variipennis carries the virus from one host to another.[3] Luckily, this disease isn’t contagious, meaning that a sick deer isn’t going to give it directly to other deer just from being around them. The virus requires a gnat to take it up from the blood for it to be transmitted to a new host.[4] Thus, most control measures to prevent the disease focus on the intermediate, the culicoides gnat. Removing standing water and spraying insecticides where the gnats tend to mate and live are currently the most effective methods of reducing the fly population and preventing infection with the EHD virus.

Theoretically, a vaccine that could be either injected or given in the feed would be very useful for protecting susceptible animals from the virus. But there are a few problems with developing one.

Firstly, the EHD virus is an RNA virus. This means that rather than its genome being made up of DNA like in animals, it is made up of RNA. There are a few structural and component differences between DNA and RNA, but the important part is the different effect that each one has. RNA is more susceptible to mutations during replication. This, combined with the incredible numbers of virus that are produced, means that the virus changes and adapts incredibly quickly. Any vaccine produced that targets specific pieces of the virus genome would rapidly be worked around.

Secondly, our vaccines to control and prevent viral infections are already limited. Due to the fact that viruses use the host’s cells to replicate, it is difficult to develop safe and effective drugs. Studying the genetic sequence of viruses helps determine what compounds would prevent their replication, but as I said, viruses (especially RNA viruses) mutate rapidly. This is the main problem with flu vaccines; new ones must be manufactured each year, as the previous year’s vaccines are ineffective due to viral mutation.[5]

There may be some steps in the EHD virus cycle that can be targeted. Host cells are very good at recognizing and eliminating viral genome, so the virus wraps its RNA in a protective coat called a capsid, so that the immune system can’t see it. Perhaps a vaccine to the capsid could be developed. This way, the body could catch the virus before it even had a chance to enter the cells, increasing safety and efficacy. Unlike other vaccines that target cell receptors, which are very specific and highly mutable, perhaps the capsid would be less changeable.

Controlling and treating viruses has been a difficult subject for decades. At the moment, the easiest way to prevent Epizootic Hemorrhagic Disease is to prevent the gnat that spreads it.


[1] https://www.michigan.gov/emergingdiseases/0,4579,7-186–26647–,00.html

[2] Given, M. D. (2018) VMED 9250 Section 9-10 Orbi Birna & Paramyxoviridae 181106 [PowerPoint slides].

[3] https://animaldiversity.org/accounts/Culicoides_variipennis/

[4] https://www.michigan.gov/emergingdiseases/0,4579,7-186–26647–,00.html

[5] https://www.medicinenet.com/flu_vaccination/article.htm#what_is_influenza_flu