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  • 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 humanitysince 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 deathhardly 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 brainmake more of itself and infect new hosts.

  • Let's see what happens if you get infected.

  • It all starts with a bite, most likely bydog 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 otherby 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 problemIt 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 virusand 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. Well 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 whilewhich 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 itselfand 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 monsterUntil 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  arrivethey 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 comaThere 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 reasonbecause  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 youve 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 monsterIt lurks in the  

  • shadows, in forests and animals of all kindsready 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. Youll 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 researchBrilliant will  

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

In the 1970s thousands of Chickenheads rained  from the sky in Europe, making foxes and other  

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B1 US rabies immune immune system infected brain system

The Deadliest Virus on Earth

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    沈恩宇 posted on 2022/08/02
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