In the 1970s, thousands of chicken heads fell from the sky in Europe, leaving foxes and other animals confused but also very happy. Why? Well, they were filled with a vaccine to combat the deadliest virus for humans. Since the 1930s, an epidemic of rabies has swept through animal populations in Europe, and humans have wanted to finally get rid of the virus once and for all.
Rabies was named after Lyssa, the ancient Greek spirit of furious madness, and has haunted us for at least 4000 years. It can turn animals into fierce beasts and humans into water-fearing zombies. What makes Lyssa fascinating is not only how bizarre and deadly this infection is, but also how adept it is at evading our defenses.
The Simple Virus
Viruses exist on the border between life and death. They are little more than genetic instructions that need living cells to multiply. The Lyssa virus is relatively simple, with only five genes that encode for five proteins. These proteins allow the virus to solve complex problems: infect a mammal, evade its immune system, travel to its brain, multiply, and infect new hosts.
When you get infected, it all starts with a bite, most likely from a dog that carries millions of viruses in its saliva, injecting them deep into your tissues. The target is the nervous system, specifically the neurons. These electrochemical cables transmit signals throughout the body, stretching up to 1.5 meters, with cellular machinery on one end and a terminal on the other. The terminal is where cells communicate with each other by exchanging chemical substances that convey information.
Lyssa likely binds to receptors crucial for this process and sneaks into unsuspecting nerve cells. Inside, the virus faces a major problem. It needs to reach the cellular machinery to take control of the cell and create more viruses. Since neurons are quite long, this can be a considerable distance to cover. Fortunately, there is a solution at hand.
Cells have microtubules running through their interiors, providing structural integrity and acting as a delivery system. Dynein motors are tiny machines that use energy to transport cargo. Made up of 50 different proteins, they resemble a pair of shoes. Lyssa utilizes one of its five proteins to hijack this incredible system and order it to travel to the nucleus.
Evading the Immune System
What does the immune system do to prevent all this? Unfortunately, not much. When a virus attacks, civilian cells are crucial as they activate the immune system response. They recognize that they have been infected and release hundreds of thousands of proteins from a particular family called interferons, which interfere with viruses.
Interferons not only alter the immune system response to create antiviral weapons, but they also tell civilian cells to shut down their protein factories for a while. This means that viruses can no longer reproduce efficiently. Additionally, interferons make cells become highly transparent. This is important because immune cells need to notice that infected cells are hiding viruses.
The body solves this problem by creating tiny windows into the interior of cells, called major histocompatibility complex class I molecules. Cells constantly produce these molecules to show immune cells what is happening inside them. They randomly sample their products and present them in these tiny windows.
Interferons instruct cells to create many more of these windows and become highly transparent. If a cell is infected and forced to create virus parts, immune cells can see these parts in one of the windows and order the infected cell to self-destruct along with any trapped viruses. This is one of the most powerful methods to annihilate a viral infection.
Unfortunately, Lyssa prevents neurons from creating interferons, rendering them invisible to the immune system. Unlike many other viruses, when it reproduces, it doesn't kill its host, which would trigger an alarm system. Instead, it stealthily jumps from neuron to neuron, slowly making its way to the brain. This phase can take weeks, months, or even years, depending on various factors such as the location of the bite and the number of viruses that entered the muscles.
Lyssa is a patient monster. It continues its journey until it reaches its ultimate goal: the brain. Eventually, the immune system realizes that something is wrong and reacts. It releases some of its most powerful antiviral cells, killer T cells, to chase and kill infected cells and destroy the enemy. In the case of a rabies infection, this would be a major turning point, but Lyssa has a trick up its sleeve.
The central nervous system is a very delicate part of the body, and the immune system must be cautious. Immune cells are not free to enter the nervous system; they must be invited and can be expelled. To protect itself, nerve cells can order T cells to self-destruct if they think they are overreacting. And Lyssa has found a way to make infected neurons give this order. So just as defense cells arrive, they are forced to self-destruct.
The virus then enters the brain stem. When this stage is reached, death is imminent.
The Mysterious Death
One of the most frustrating things about the Lyssa virus is that we still don't know exactly how or why an infected person dies. Our usual idea is that viruses cause damage by rapidly multiplying and killing their host once they have made enough copies. This triggers a massive immune response that also causes significant damage. However, this doesn't seem to be what happens with Lyssa.
The brain tissue of rabies patients shows minimal or virtually no damage. Instead of killing outright, Lyssa seems to wreak havoc by disrupting communication between neurons to such an extent that the brain can no longer function properly. This attack on the brain leads to symptoms such as confusion, aggression, and paralysis.
Meanwhile, the virus continues migrating through neurons, moving away from the brain and heading towards the salivary glands. This is remarkable because after traveling in one direction, the virus reverses its course. After decades of study, we still don't know how this works.
Lyssa eventually saturates the saliva, ready to repeat the cycle when an irritated mammal bites another living being. Although this may sound like the beginning of a zombie outbreak, there have fortunately been no reported cases of humans biting others and spreading rabies in this way.
The end is near. The victim develops encephalitis, swelling of the brain accompanied by various unpleasant pathological symptoms, from lethargy to paralysis. Slowly at first, and then suddenly, one organ after another begins to fail as the victim slips into a coma. There is no known effective treatment, and almost no one has survived once Lyssa symptoms begin to appear. It is by far the deadliest virus we know.
The Vaccine
Except for one thing that can save lives - a vaccine. Rabies was one of the first diseases for which humans developed a vaccine. Like any vaccine, it prepares the immune system for a future attack, ensuring that it has the right weapons ready in large numbers. The cunning tricks of simple Lyssa no longer work when a person is vaccinated.
Furthermore, the vaccine is special for another reason. Because Lyssa is slow during the first weeks, the vaccine can be given after exposure. It is possible to be vaccinated after being bitten by an animal. This is crucial if there has been contact with a sick animal, such as a bat, as it is often difficult to notice a bite from tiny teeth.
Rabies is a monster that has haunted our species for thousands of years, terrifying our ancestors for good reason. It still kills about 60,000 people each year, with approximately half of them being children. We are far from eradicating this monster; it lurks in the shadows, in forests and in animals of all kinds, ready to come back in force if we ever forget how to keep it at bay or continue to be suspicious of vaccines.
Hopefully, one day humanity will conquer this monster and it will become, like most monsters, a part of our imagination. There is much more knowledge to explore, and rabies is just a glimpse of what we have shown you. But delving into scientific sources and information can be intimidating. That's why we have partnered with our friends at Brilliant to create an interactive course with practical lessons to guide you through some of the concepts shown in this video.
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