In the 1970s, thousands of Chickenheads filled with a vaccine to fight the deadly rabies virus rained from the sky in Europe, making foxes and other wildlife confused and very happy. Rabies is named after Lyssa, the ancient Greek spirit of mad rage, and has been around for at least 4000 years. It can turn animals into angry beasts and humans into zombies that fear water.
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. 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.
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, which are living electrochemical wires, transferring signals throughout your body. 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. 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, 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. 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, making it invisible to your immune system. Replicating slowly, it jumps from neuron to neuron, making its way to your brainstem, which can take weeks or months, or even years, depending on the location of the bite. Lyssa is a patient monster, and when it reaches its goal, the immune system finally reacts. It dispatches Killer T Cells to seek and kill infected cells, but Lyssa has a trick up its sleeve. It can make infected neurons express an order for the T Cells to self-destruct, protecting itself from the immune system. As the Killer T Cells arrive, they are ordered to commit suicide, allowing the virus to infiltrate the brain stem, where the infected person will eventually die. It is currently thought that Lyssa wreaks havoc by messing up the neuron communication inside the brain, so much so that it can’t function anymore. It then migrates away from the brain and heads for the salivary glands, ready for the next mammal to bite, repeating the cycle.
Fortunately, there is a vaccine that can prevent Lyssa from taking hold. It prepares the immune system for a future attack, so it has the right weapons ready in high numbers. The horrific tricks of Lyssa don’t work once you are vaccinated, and it can even be given to you after you have been exposed. Therefore, it is possible to be vaccinated after being bitten by an animal. It is extremely important to be aware of the dangers of rabies if you have had contact with a sick wild animal, such as a bat, as it is often hard to notice a bite from small teeth. Rabies is a dangerous virus which has been around for thousands of years and still kills around 60,000 people each year, with nearly half of those being children. We are still far away from eradicating this virus, as it hides in the shadows and in wild animals, ready to return if we overlook it or are suspicious of vaccines. We can only hope that one day humanity will be able to defeat this monster and it will become like other monsters, part of our imagination.
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