In the 1970s thousands of Chickenheads rained
from the sky in Europe, making foxes and other wildlife confused and very happy. Why? They were
filled with a vaccine to fight the deadliest virus known to humanity – since the 1930s
a rabies epidemic had been sweeping across wildlife populations in Europe and humans wanted
to finally get rid of the virus once and for all. Rabies is named after Lyssa, the
ancient Greek spirit of mad rage, and has been haunting us for at least 4000
years. It can turn animals into angry beasts and humans into zombies that fear water. But
what makes Lyssa fascinating is not just how bizarre and deadly its infection is, but also how
incredibly good it is at avoiding our defenses.
Viruses exist on the edge between life and death,
hardly more than a few genetic instructions that need living cells to multiply. The lyssavirus is
simple even for a virus: It has only five genes, that is the instructions for five proteins that
let it solve complex problems: Infect a mammal, avoid its immune system, travel to its brain,
make more of itself and infect new hosts. Let's see what happens if you get infected. It all starts with a bite, most likely by a
dog carrying millions of viruses in its saliva, pushing them deep into the tissue. The goal is
your nerve cells, your neurons. They are living electrochemical wires, transferring signals
throughout your body, and can stretch for up to 1.5 meters, with their cellular machinery
on one end and a terminal on the other. The terminal is where cells talk to each other,
by passing chemicals that convey information. Lyssa probably binds to the receptors
that are crucial for this process and slips inside the unsuspecting nerve cells.
Inside, the virus has to solve a big problem.
It needs to get to the cellular machinery to take over the cell and make more viruses
– and because neurons are pretty long, this can be far away. There
is a solution at hand though: Cells have microtubules spanning their
insides that give them structural integrity. But they also provide a track system
for a specialized delivery system: Dynein motors are actual motors that use energy
and deliver packages. They are made from 50 different proteins, ten times more than the virus,
and look like a little pair of shoes.
Lyssa uses one of its five proteins to hijack this amazing
system and order it to head for the nucleus. What is the immune system doing to prevent
all of that? Well, unfortunately not much. Usually when a virus attacks your civilian cells
are crucial in activating your immune response. They notice that they have been infected and
release hundreds of thousands of a special family of proteins: The interferons that, well, interfere
with viruses. We’ll have to simplify a lot, but in a nutshell, Interferons alert your
immune system to make antivirus weapons. But they do much more: they tell civilian
cells to turn down their protein factories for a while – which means that viruses
can’t replicate efficiently anymore.
And interferons tell your cells to become super
transparent, which is important, because how can your immune cells notice that your civilian
cells are infected when viruses hide inside them? Your body solves this by creating display windows
into their insides, called MHC class I molecules. Cells constantly produce stuff to stay alive, and to showcase to your immune cells what is
going on inside them, they take random samples of their products and put them into these
tiny display windows to give a peek inside.
Interferon tells your cells to make WAY more
display windows and become super transparent. If a cell is infected and forced to make virus
parts, your immune cells will see these parts in a window and order the infected cell to
kill itself – and all the viruses trapped within. This is one of the most powerful
methods of wiping out a viral infection. Unfortunately Lyssa blocks your neurons
from making interferons and stays basically invisible to your immune system. In contrast
to many other viruses, when it replicates, it doesn’t kill its host, which
would also trigger alarm systems. Instead it stealthily jumps from neuron to
neuron, very slowly making its way to your brain. This phase can take weeks to
months and very rarely even years and depends on a bunch of things, like if the bite
was in your face or foot or how many viruses got into your muscles. Lyssa is a patient monster.
Until it reaches its goal: Your brainstem. Finally, the immune system catches
on that something isn’t right and reacts. It dispatches some of your most
powerful antivirus cells, Killer T Cells, to seek and kill infected cells and wipe out the
enemy.
