The Starting Point: A Bite#

It usually starts with a bite, most likely from a dog that’s carrying millions of viruses in its saliva. When it bites, it pushes these viruses deep into the tissue.

Targeting Neurons#

The virus has a specific goal: your nerve cells, also called neurons. Think of neurons as living electrical wires that send signals all over your body. They can be really long – up to 1.5 meters (about 5 feet)! Each neuron has its main cell body (with all the machinery) at one end and a terminal at the other.

The terminal is where neurons talk to each other by passing chemical messages. Lyssa seems to grab onto the spots on these terminals that are important for this communication (receptors) and then sneaks inside the unsuspecting nerve cell.

The Long Journey: Hijacking Cell Machinery#

Once inside, the virus has a big problem. It needs to get to the neuron’s main cell body to take over and make more viruses. Since neurons can be super long, this destination can be quite a distance away.

Luckily for the virus (but not for you!), cells have a built-in solution. Inside, cells have structures called microtubules. These act like internal scaffolding for the cell, giving it shape. But they also work as a track system for a special delivery service.

Enter the dynein motors. These are actual motors within your cells! They use energy and are designed to carry packages from one part of the cell to another. These motors are pretty complex themselves, made from 50 different proteins (ten times more than the virus has!). They even look a bit like tiny pairs of shoes.

Lyssa uses just one of its five proteins to hijack this amazing system. It essentially tells the dynein motors to grab onto the virus and head towards the neuron’s control center – the nucleus (where the cell body is).

The First Line: Blocking Interferons#

Normally, when a virus attacks, your everyday cells (your “civilian” cells) are key to kicking off an immune response. They sense they’re infected and release tons of special proteins called interferons. As the name suggests, interferons interfere with viruses!

We have to simplify this a lot, but basically, interferons do a bunch of things:

• They alert your immune system to start making “antivirus weapons.”
• They tell healthy civilian cells to slow down their protein-making factories. Why? Because viruses need these factories to build copies of themselves, so slowing them down makes replication much harder for the virus.
• They tell your cells to become “super transparent.” This is important because how can your immune cells spot a hidden virus inside another cell?

Your body has a clever way to show what’s going on inside cells. Cells constantly produce things to stay alive. To give your immune cells a peek, they take random samples of whatever they’re producing and put them into tiny “display windows” on their surface called MHC class I molecules.

Interferons tell your cells to make way more of these display windows, essentially making them super transparent. If a cell is infected and forced to make virus parts, your immune cells patrolling the outside will see these viral parts in the MHC class I window. When they see this, they order the infected cell to self-destruct, hopefully killing all the viruses trapped inside too. This is one of your body’s most powerful ways to clear a viral infection.

Unfortunately, Lyssa blocks your neurons from making interferons. This means the virus stays basically invisible to your immune system in these early stages.

Also, unlike many other viruses, when Lyssa replicates, it usually doesn’t kill the neuron immediately. Killing the host cell would trigger immune alarms. Instead, it stealthily jumps from neuron to neuron, very slowly making its way towards your brain.

This quiet travel phase can take weeks to months, and sometimes even years, depending on things like where the bite was (face vs. foot) or how many viruses got into your muscles. Lyssa is a patient monster.

The Clever Trick: Turning T Cells Away#

This slow, stealthy journey continues until it reaches its ultimate goal: your brainstem.

Finally, deep inside the nervous system, the immune system starts to catch on that something serious is wrong and reacts. It sends in some of your most powerful antivirus fighters: Killer T Cells. Their job is to find and kill infected cells and wipe out the enemy.

In most other viral infections, this would be the turning point where your body starts winning. But with rabies, these T cells are often rushing towards their doom.

Simple Lyssa, with its mere five proteins, plays a kind of “uno reverse card,” using the immune system’s own clever rules against it.

Your central nervous system (brain and spinal cord) is super sensitive and fragile. Because of this, the immune system has to be very careful inside it. Just a few out-of-control immune cells could quickly cause fatal damage. So, immune cells aren’t freely allowed to roam in your nervous system. They have to be invited in and can be kicked out.

To protect themselves from potential friendly fire, your nerve cells can actually order T Cells to self-destruct if they think the T cells are overreacting or causing harm. And guess what? Lyssa figured out a way to make infected neurons express this exact order.

So, as your powerful defense cells arrive, ready to fight, they are essentially told to commit suicide instead.

Now the virus has infiltrated the brainstem, a critical part of your brain. Once it reaches this stage, sadly, it’s almost certain you are going to die.

The Mystery of How it Kills#

One of the most frustrating things about the Lyssavirus is that, even after all these years of study, we still don’t know exactly how and why an infected person dies.

Our usual understanding of viruses causing death is through multiplying rapidly, killing their host cells, and triggering a huge immune reaction that also causes a lot of damage. But this doesn’t seem to be what happens with rabies. When doctors look at the brain tissue of rabies patients, they find minimal, sometimes even non-existent, damage to the brain cells themselves.

Instead of just murdering everything, the current thinking is that Lyssa causes chaos by severely messing up the communication between neurons in your brain. It disrupts the signals so badly that the brain just can’t function properly anymore.

This attack on the brain leads to severe symptoms like confusion, aggression, and paralysis.

Preparing to Spread: The Saliva Journey#

Now, the virus begins a remarkable next phase: it starts to leave the brain. Still traveling through neurons, it migrates away from the brain and heads towards the salivary glands. This is truly remarkable – after traveling in one direction to reach the brain, the virus somehow reverses course! After decades of study, we still don’t understand how this reversal works.

Lyssa ends up flooding your saliva, getting ready for the now-irate mammal (like a dog or a bat) to bite someone else and repeat the whole terrible cycle.

While this sounds like the start of a zombie movie, luckily, there are no known cases of a human biting another human and spreading rabies this way.

The Final Symptoms and Outcome#

At this point, the end is near. You rapidly start developing encephalitis, which is a dangerous swelling of the brain. This causes many awful neurological symptoms, from just feeling tired and sluggish (lethargy) to complete paralysis.

Slowly at first, and then suddenly, your organs start to fail one after another, and you slip into a coma.

There is currently no known effective therapy once symptoms begin to show. Barely anyone has ever survived rabies once the symptoms have appeared. It is, by far, the deadliest virus we know.