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Why Scientists Are Puzzled By This Virus


7m read
·Oct 29, 2024

Very recently, scientists discovered that your body is teeming with trillions of the most bizarre viruses. These viruses are not your enemies but critical to your health, protecting you from disease, maybe even killing cancer. A new frontier of science, something truly new that we are only just beginning to understand. Let us dive into the wild world of the human virome.

You are an Ecosystem. You're a living, breathing ecosystem made of up to 40 trillion cells. This metropolis of flesh is home to the human microbiome, another 40 trillion bacteria that have a contract with your body: They get to live here and in return, they break down your meals. They synthesize vitamins in your gut, neutralize acid in your mouth, help balance your immune system, and they take up space, preventing harmful bacteria from getting in. This is a fragile balance – bacteria really only look out for themselves, multiplying and testing their boundaries. To keep their numbers in check, your body's ecosystem needs a group of deadly predators: Viruses.

At least ten trillion. They're literally everywhere in your body, tens of thousands of different species. At least a few trillion live in your gut, where also most of your resident bacteria are. At least 18 billion on your skin, 100 million in each drop of your saliva, dozens of millions in your urinary tract. Even in a single drop of the cerebrospinal fluid surrounding your nerves and brain, researchers found up to 10,000 viruses. While this sounds like a horrible idea at first, at least in the gut, around 97% of them are bacteriophages, or phages, bizarre creatures that are specialized in hunting down and killing resident bacteria and are not able to infect your cells. Instead, they kill trillions of bacteria every single day.

Together, these viruses make up the human virome – a symbiotic virus ecosystem that is completely unique to you and that seems to be crucial for your health. Let’s get to know them and see how they support you – and what happens if things go wrong.

The Silent Mass Murderers of Your Body. Inside your gut, a stealthy Lambda Phage floats through the buzzing crowds of bacteria, looking for a victim. It has six legs, a long thin body, and a big head made of geometric shapes, filled with genetic material. Each species is specialized in hunting one specific species of bacteria and ignores all others. Lambda is looking for Escherichia coli. This versatile bacteria is numerous in your gut, usually a good boy synthesizing vitamins for you. But it also has a dark side – some of them would much rather live inside your flesh and feast on your resources. If there are too many or if they manage to invade your tissue, they can cause serious diseases.

So one of the most important jobs of the virome is to control the numbers of different bacteria populations by killing them. Lambda has found a victim. Spider-like legs get a hold of a bacteria and grip it hard. Like an angry syringe, it violently rams its sharp bottom into the victim’s body and releases its DNA. Once inside, the proteins disable the defenses of the bacterium. It is now a factory under new management. It is forced to build new viruses until the victim is filled up and bursts open, releasing a horde of fresh Lambda viruses. But its goal is not genocide. Phages need a healthy population of bacteria to survive.

So sometimes they choose a way more sinister tactic. Instead of killing their victim, the virus integrates its DNA into the genome of the bacteria and goes to sleep. When the bacteria multiplies, the virus DNA is multiplied too. Until one day, the viral DNA re-awakens and suddenly decides to kill its unsuspecting victim. And here things become exciting – your virome also needs you to thrive. It’s in its best interest that you are healthy. So some viruses inject genes into bacteria that actively make them support your body. Some force their bacteria hosts to support your gut’s mucus layer, break down complex carbohydrates from your food more efficiently, creating substances that protect against inflammation. And they alter what signals bacteria send to your immune cells. Basically, they’re letting them know: We have things under control, you can chill out. This may prevent allergic reactions or even protect you against autoimmune diseases.

But of course, there is also a dark side to this story. Some viruses don’t care about our health. Instead of helping, they turn harmless bacteria into deadly monsters. When Viruses turn Bacteria into killers, some species of bacteriophage carry dangerous genes for toxic substances. When they take over their hosts, they can integrate into the genetic code of the bacteria where they lay as a deadly gift. Like the case of the Vibrio cholerae and the CTXφ bacteriophage hunting them.

Most strains of the cholerae bacteria are harmless, and billions of them may live in your gut right now. When CTXφ infects the bacteria, they gift them the genes for the cholera toxin, which permanently becomes part of their genetic lineage forever. It's like handing a house cat a shotgun. Vibrio cholerae shower these toxins at the cells lining your gut, making them sick. They vomit large amounts of salt, which pulls out a flood of water into your intestines. This causes explosive diarrhea and vomiting, draining your body of fluid. If untreated, about half of patients die.

But for the phage and bacteria, this is great. They are carried out of the body to infect more humans, spreading and multiplying further. This strain of Vibrio cholerae is now a dangerous enemy of humanity, thanks to this virus. Or the bacteria Staphylococcus aureus, which is hunted by the phage with the amazing name: φSa3ms. Usually, the bacteria is mostly harmless and lives on your skin and inside your nose. It doesn’t do anything useful per se; its main job is to take up space, making it harder for hostile bacteria to colonize your body.

But φSa3ms can change this quickly – it carries multiple dangerous genes, like giving a cat flamethrowers and grenades. If such a modified Staphylococcus aureus bacteria gets into your body through a tiny cut, it becomes extremely dangerous. One of its new weapons are superantigens, which basically is like injecting your immune cells with cocaine. The toxin completely breaks your carefully fine-tuned immune system. It activates all of your T cells, all at once, and makes them flip out. They release a tsunami of cytokines, activating all of your defenses at once. The infection is flooded with cells that can’t fight the bacteria and cause heavy inflammation.

Your broken and confused immune cells have a really hard time fighting Staphylococcus aureus, which now invades, penetrating deep into your tissue. Your body is trying to seal the wounds and isolate the invader, but another new weapon it gained has the ability to just dissolve the barriers and penetrate even deeper. Before the onset of antibiotics, an infection with Staphylococcus aureus was very deadly, and we have φSa3ms to thank for making it even deadlier.

But the viruses of our virome may also directly save your life – by killing cancer. Cancer Killing Viruses. Oncolytic viruses specialize in hunting and killing cancer – like the Newcastle Disease virus or the Reovirus, which mostly ignore your healthy cells and instead hunt down tumors. Cancer cells are broken mutants that evolve various ways to hide and fight back against your immune system. But as they get better at this, they get worse at other things, like fighting back viruses. A weakness to be exploited.

Oncolytic viruses target the specific adaptations of cancer cells, hitting them where they are not ready to be hit. And worse for these cells, since their internal machinery is compromised, they can’t defend themselves. They are taken over and turned into virus production factories. Eventually, the new viruses leave the cancer cell, often killing it, and carry on infecting other cancer cells nearby. This death and destruction is not subtle, and one side effect is that it attracts immune cells that immediately begin attacking the tumor with full force.

What is even more impressive is that these viruses seem to disrupt the artificial environment that tumors create to keep your immune system at bay. Oncolytic viruses are like infiltrators in a city at siege, opening the gates while killing defenders left and right – helping your immune cells to win the fight.

In 2024, we don’t know yet to what degree oncolytic viruses are part of your virome or more of a happy accident. But they seem to go well together with chemotherapy or radiation. Eventually, they may become an important new tool to enable us to eliminate cancer and save millions of lives. We don’t know what we will learn in the next few years, but we now know that there are trillions of potential allies within us, killing and manipulating, for better or worse. What an exciting time to be alive.

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