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. In other viral infections this would be a  

turning point, but in rabies the T cells are  rushing towards their doom. Simple Lyssa with  

its 5 proteins plays a uno reverse card, using  the immune system's ingenuity against itself.

Your central nervous system is a very fragile  part of your body and so the immune system has  

to be very careful. A few haywire immune  cells in your brain is a quick way to die.  

So they aren't free to enter your nervous  system, they have to be be invited in  

and can be kicked out. To protect themselves, your  nerve cells can order T Cells to self-destruct,  

if they think they are overreacting. And Lyssa  figured out a way to make infected neurons express  

this order. So as your powerful defense cells  arrive – they are ordered to commit suicide.  

Now the virus infiltrates the brain stem. Once  this stage is reached you are going to die.

How Lyssa Kills

One of the most irritating things about  the Lyssavirus is that we still don't  

know exactly how and why an infected person dies.

Our usual idea of viruses causing  damage is by multiplying rapidly,  

killing their host cells once they have made  enough copies, triggering a massive immune  

reaction that also does a lot of damage. But  this doesn't seem to be what happens here.  

Brain tissue of rabies patients shows  minimal, sometimes non-existent damage. 

Instead of murdering everything in sight, it  is currently thought that lyssa wreaks havoc  

by messing up the neuron communication inside your  brain, so much so, that it can't function anymore.

It attacks the brain and leads to symptoms  like confusion, aggression and paralysis. 

Now the virus begins to leave. Still traveling  through neurons, it migrates away from the brain  

and heads for the salivary glands. This is  remarkable, because after traveling in one  

direction the virus reverses its course. After  decades of study we don't know how this works.  

Lyssa ends up saturating your saliva  ready for the irate mammal to bite another  

and repeat the cycle. While this seems  like the beginning of a Zombie outbreak,  

luckily there are no known cases of a human  biting another and spreading rabies this way.

Now the end is near. You are rapidly developing  encephalitis, a swelling of the brain with many  

unpleasant neurological symptoms, from lethargy  to paralysis. Slowly at first, and then suddenly,  

organ after organ fails as you slip into a coma.  There is no known effective therapy, barely anyone  

has ever survived Lyssa once symptoms begin to  show. It is by far the deadliest virus we know.

Except, there is actually something  that could save you – a vaccine.  

Rabies was one of the first diseases  humans developed a vaccine for.  

As vaccines do, it prepares your immune system for  a future attack, so it has the right weapons ready  

in high numbers. The horrific tricks of simple  Lyssa don't work once you are vaccinated. And the  

vaccine is special for another reason – because  Lyssa is so slow in the first few weeks, it can  

be given to you after you have been exposed. So  you can still be vaccinated after you have been  

bitten by an animal. Which is super important  if you've had contact with a sick wild animal,  

say a bat, because you often don't  even notice a bite from tiny teeth.

Rabies is a monster. One that has followed  our species around for thousands of years,  

that our ancestors were terrified of and rightly  so. It still kills around 60,000 people each year,  

almost half of them children. We are far from  eradicating this monster – It lurks in the  

shadows, in forests and animals of all kinds,  ready to return in greater numbers if we ever  

forget how to keep it at bay, or if we continue  the trend of being suspicious of vaccines.

Let us hope that one day  humanity slays this monster,  

so it can become like most  monsters: Part of our imagination.

There are much deeper levels  of knowledge to explore about  

rabies than the glimpse we just showed you.

But digging into sources and  scientific information on your own  

can be intimidating. So we partnered with our  friends from Brilliant to create an interactive  

course with hands-on lessons to guide you through  some of the concepts we showed in this video.  

Brilliant is an interactive learning  tool with over 60 courses in math,  

science, and computer science. They make  science accessible with a hands-on approach.  

Think of it as a one-on-one tutoring version  of a Kursgesagt video. You'll experiment with  

how fast the virus can reach your brain based on  its protein makeup or run simulations on Rabies'  

genetic evolution, to explore how mutations  created the deadly virus we know today.

You can do things like manipulate energy  to see how black holes are formed,  

or control the expansion of space itself to  determine the ultimate fate of the universe.

To get some behind-the-scenes-science-coaching  on space and biology and many more topics,  

go to Brilliant.org SlashNutshell and sign  up for free. And there's an extra perk for  

kurzgesagt viewers: the first 200 people to use  the link get 20% off their annual membership,  

which unlocks all of Brilliant's courses  in math, science, and computer science.

We love to go down a rabbit hole  with our research – Brilliant will  

take you by the hand to come along on the ride.