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  • Alex Cloherty

Think like a virus

After a few weeks off due to #PhDLife, Microbial Mondays is back with a question from Sarah! Sarah said, "I'd be super interested to learn more about genes derived from genetic parasites being involved in our cognitive functioning." Let's dive in.


Sarah asked this question after reading this Microbial Mondays post, where I wrote about how we can not only learn to live with our genetic parasites, but they can actually become an intrinsic part of us. More specifically in humans, genes derived from genetic parasites are involved in core biological processes that make us who we are - such as placenta formation, cognitive functioning, and even immune defense. If these parasites hadn't crept into and altered our genomes, we would not be who we are today.


In terms of genetic parasites supporting our cognition, I was specifically referring to one protein that was simultaneously described by two independent research groups (from New York and Massachusetts) in 2018: the "Arc" protein.


It has been known for a while that the Arc protein is pretty darn important. For example, Arc has been called a "master regulator of synaptic plasticity in mammals". What that means, is that Arc helps your brain to change. Your brain is made up of a lot of different cells called neurons, and those neurons have to be able to talk to each to drive the complicated behaviours and processes that make us human. Neurons talk to each other by communicating across spaces between neighbouring neurons that are called synapses. The differential strength of the communication between neurons, at those synapses, is one of the more concrete underpinnings of things like learning and memory. Put simply, depending on how strong or weak that communication is, it's easier or harder for neurons to talk to each other. In the case of memory, that can mean, for example, that it's easier or harder to remember something. What scientists mean when they call Arc a "master regulator of synaptic plasticity", is that Arc helps to control the strengthening and weakening of neuronal communications.


And, on top of helping to regulate the structural underpinnings of learning and memory in your brain, scientists have also found that Arc plays some role in a multitude of different brain disorders, from Alzheimer's disease to schizophrenia. All this is just to say that Arc is a very important protein indeed.


But how does this relate to viruses?


Well, to discover the answer to that question, scientists first had to dive into how Arc works. One of the ways that the Arc protein regulates that ongoing strengthening and weakening of communications between neurons, is by shuttling information back and forth between neurons. Basically, Arc can act as a shuttle that carries messages from one brain cell to another, and those messages tell the two brain cells how they can interact with each other. But interestingly, the way that Arc shuttles those messages looks an awful lot like how viruses "shuttle" from one cell to another.


When a specific class of viruses called "retroviruses", which includes big names like HIV, infect cells, they get out again by rebuilding many new copies of themselves - the mama virus that infects a cell will make lots of new baby viruses. One of the many steps that are important in building these new baby virus copies, is the formation of a "capsid" - basically a ball of virus protein with some genetic material inside. To build a "capsid", the mama virus will direct the production of many identical subcomponents that come together to create a globe of protein that will encapsulate all of the information (the genetic material, kind of like our DNA) needed to make the next generation of baby viruses. You can imagine the process as Lego self-assembling into a Lego car that has the Lego blueprint for how to build more Lego cars contained inside it. In the end, viruses are pretty much just a blueprint contained within in a ball of protein (and sometimes that ball of protein is covered with fat). And so, a daughter virus is born.


The cool thing about Arc, is that it self-assembles in a way that is strikingly similar to retroviruses. Lots of identical Arc proteins will come together to make a globe of protein that will encapsulate information that needs to be sent from one neuron to another. When viewed in super-high powered microscopes, that protein globe of Arc suspiciously looks very much like HIV capsids. Then, those Arc "capsids", or protein globes, that are composed of lots of copies of Arc, then are able to exit the neuron in a way similar to how retroviruses exit their infected host cells. And finally, the Arc "capsids" enter into a neighbouring neuron in a way that mirrors how viruses enter cells.


It was the two research groups (this one and this one) that I mentioned at the beginning of this post that first showed that Arc functioned in this virus-like manner. The authors of those papers show that many different actions of the Arc protein are remarkably similar to the structural proteins of retroviruses - and suggest that that is probably indeed where Arc came from. The authors speculate that viral genes "have been… co-opted to participate in… intercellular trafficking of RNA in the nervous system". In other words, we made some viral genes our own, and put them to work.


The authors also note that it could be the other way around - maybe Arc came first, and viruses stole our genes for their benefit. But either way, it is a fascinating case of trading genes between us, the hosts, and our invaders, the viruses.


So, if you feel like you've learned something, or if you remember this information tomorrow, you know who you have to thank. Probably, a virus.


Until next week, don't stop learning!

~Alex


All of the information in this Microbial Mondays post is based on information drawn from these two articles:


https://www.cell.com/cell/fulltext/S0092-8674%2817%2931504-0#secsectitle0095

https://www.cell.com/cell/fulltext/S0092-8674(17)31502-7#secsectitle0075

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