The memory virus

It's virus season, which thus far I've been able to avoid participating in, but every time I go to the grocery store I see people who are hacking and snorting and coughing and I figure it's only a matter of time, despite my insistence on wearing a mask in public.  Viruses are odd beasts; they're obligate intracellular parasites, doing their evil work by hijacking your cellular machinery and using it to make more viruses.  Furthermore, they lack virtually all of the structures that cells have, including cell membranes, cytoplasm, and organelles.  They really are more like self-replicating chemicals than they are like living things.

Simian Polyoma Virus 40  [Image licensed under the Creative Commons Phoebus87 at English Wikipedia, Symian virus, CC BY-SA 3.0]

What is even stranger about viruses is that while some of the more familiar ones -- colds, flu, COVID, measles -- invade the host, make him/her sick, and eventually (with luck) are cleared from the body -- some of them leave behind remnants that can make their presence known later.  This behavior is what makes the herpes family of viruses so insidious.  If you've been infected once, you are infected for life, and the latent viral genetic material hidden in your cells can cause another eruption of symptoms, sometimes decades later (as I found out the hard way when I got shingles a couple of years ago).

Even weirder is when those latent viral remnants cause havoc in a completely different way than the original infection did.  There's a piece of a virus left in the DNA of many of us called HERV-W (human endogenous retrovirus W) which, if activated, can trigger multiple sclerosis or schizophrenia.  Another one, Coxsackie virus, has an apparent connection to type-1 diabetes and Sjögren's syndrome.  Thus far, all of the viral infections, whether or not they're latent, are damaging to the host.  So it was quite a shock to me to read a piece of recent research that there's a viral remnant that not only is beneficial, but is critical for intercellular communication -- and individuals without it have trouble forming long-term memories!

In two separate papers published in the journal Cell -- "The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer" and "Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics Across Synaptic Boutons," each by a large team of neurobiologists and geneticists -- we learn about the proteins Arc and Gag, which were put into our cells by retroviruses (probably) hundreds of millions of years ago, and which generate virus-like particles that transfer from one brain cell to another.  This process seems to mediate memory formation, as mice that have the Arc/Gag gene knocked out are unable to retain long-term memories -- and may even be unable to form them in the first place.

As Sara Reardon explained it, writing in Nature:

Shepherd and Budnik [lead researchers in the two studies] think that the vesicles containing Arc play a part in helping neurons to form and break connections over time as an animal’s nervous system develops or adapts to a new environment or memory.  Although the fly and mouse versions of Arc are similar, they seem to have evolved from two distinct retroviruses that entered the species’ genomes at different times.  "There must be something really fundamental about it," Budnik says, for it to appear in both mice and flies... 

The human genome contains around 100 Gag-like genes that could encode proteins that form capsids.  It’s possible that this new form of communication between cells is more common than we thought, Shepherd says.  "We think it’s just the beginning."

Which is pretty astonishing.  The idea that some viruses might have beneficial effects on the host is weird enough; the idea that they could facilitate something as basic as memory storage is mind-blowing.  As such, they'd be a major driver for evolution -- given that organisms that have strong memory capacity are clearly at an advantage over ones that don't.

So before you curse the viruses this winter, be a little thankful for Arc and Gag and any other genetic parasites we might have that help us to function.  It may be small consolation if you are currently fighting a cold, but keep in mind that without viruses, you might not be keep anything in mind at all.

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