How Viruses Work, part 2: Replication Basics
By: Julia Daniel
Tags: Biology, Covid 19, Infectious Disease, Virus, Central Dogma

I wrote yesterday that viruses, for all the hype and damage, are incredibly simple. They have no internal life of their own, no grand premeditated strategy, no way to eat or breathe or move or mate or do anything else worthwhile and fun. There is one thing they are very good at, though, and that is having copies made of themselves.

We’re always told to avoid passive voice (hah), but I’m wary of saying that viruses really do anything. As I described yesterday, they have no will or tools with which to exercise agency, yet we anthropomorphize them ceaselessly. Just like the gum on my shoe didn’t scheme about how it would use me to cross the city, viruses don’t plan ahead — rather, by virtue of their simple but selected-for physical/chemical characteristics, they find themselves on doorknobs, in sewers, in crops, in aerosols, on the Space Station, in the ocean, and in all of our bodies.

Why are they everywhere, without even trying? Because they are the best machine ever made to be replicated. And when the thing you’re good at is being copied, you end up everywhere.

So let’s dig into how the virus structure makes it the perfect copyable machine.

Entering the cell: perfect matches and getting slurped

You’re out in the world and you touch a doorknob and then your face, or you eat something contaminated, or you contact infected bodily fluids. One way or another, there’s now some virus in your body. Human bodies are pretty excellent environments for the viruses we care about, so the virus particles float around being inert and unaware. They bump into and bounce off of things and some of them are picked off by immune cells patrolling for foreign objects.

In this blind bumping around, some of them run into cells that have proteins on their surface that exactly complement the proteins on the virus’ surface. For SARS-CoV-2, that’s the spike protein (on the virus side) matching up with the ACE2 protein (on the cellular side). For HIV, for another example, that’s the virus’ envelope protein matching up with the CD4 protein found only on T-cells (immune cells), which is why HIV causes immunosuppression.

This unlocking action, using the virus’ own surface as the key, then allows the virus to enter the cell through one of two ways: either forcing itself in or triggering the cell to surround it and essentially slurp it up. Good times.

Reproducing: shamelessly hijacking your body

Once a virus is inside a cell, the envelope and capsid fall apart (a process called uncoating) and the virus’ genetic material is exposed to the cell’s internal machinery. Viruses use the same means of storing genetic information as humans do — either DNA or RNA, depending on the type of virus — so there’s plenty of ready-made chemical processes ongoing in the cell that automatically pick up the viral genome as though it were human and set to work reading, copying, and interpreting it.

There’s many incredible aspects to this detailed concert of chemical interactions, but I’ll keep it brief for now. Two main things need to happen: one, the genome needs to be read and translated into the proteins that make up the capsid and, in some cases, any other auxiliary proteins in the virion. And two, the genome itself needs to be copied.

Cell machinery does both of these tasks easily and automatically, until the inside of the cell is a soup of virus parts and pieces. With a few tricks of chemistry, the newly-made virus parts reassemble themselves in a stable configuration — new virus particles.

Leaving the cell: thank u, next (possibly ft. murder)

As a final farewell, new viruses have two options for exiting the cell and going elsewhere in the body: naughty and nice. Either they gently bud out of the virus, often picking up some pieces of the cell’s membrane along the way — or they burst forth Alien-style, leaving the host cell dead. Either way, a new generation of mindless copying machines has been released into the body. If one of them runs into another cell and is able to enter it, the process starts all over again — and if the new virus particles are expelled out into the environment, such as via a cough or sneeze, then there’s the possibility of infecting a whole new host.

So without any intention at all, but with a chemical makeup that’s a perfect match for certain cells and certain cell components, viruses have been able to proliferate in amounts far beyond the amount of all cellular life, combined.