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I've been reading about viral vectors and am looking to incorporate it into my setting. From what I can see, it's possible to use viral vectors as a form of gene therapy, and retroviruses can work pretty well for these: https://www.genetherapynet.com/viral-vector/retroviruses.html

I don't understand the exact mechanics behind it, but essentially the retrovirus, with its genetic material being RNA molecules, would introduce its RNA molecules into the host's DNA.

There are some issues with this, from what I read: "the integrase enzyme can insert the genetic material of the virus into any arbitrary position in the genome of the host; it randomly inserts the genetic material into a chromosome. If genetic material happens to be inserted in the middle of one of the original genes of the host cell, this gene will be disrupted (insertional mutagenesis). If the gene happens to be one regulating cell division, uncontrolled cell division (i.e., cancer) can occur."

So - this can lead to cancer, specifically leukemia (occurred in some children in Europe IIRC).

Now, what I want to do is use this method to somehow make an airborne disease. Let's say that a genius biochemist is trying to treat his dying child and comes up with a form of retroviral gene therapy, but it goes wrong and wreaks havoc. The virus turns into a deadly, contagious airborne disease.

How could this potentially occur?

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Very easily

I don't understand the exact mechanics behind it, but essentially the retrovirus, with its genetic material being RNA molecules, would introduce its RNA molecules into the host's DNA.

Not exactly. RNA cannot be introduced into DNA, after all, they're two different structures, not to mention that they use different sets of bases. What happens is that the DNA is overwritten by the RNA template. It's a subtle, but occasionally important distinction. (Not here, though, just clarifying how it works.)

Now, if the genius biochemist decided to make make the retrovirus airborne, that solves the problem. Contagious airborne viruses do exist, such as the common cold. So that's the easy solution - the safest method was an airborne spray, and the doctor thought it was safe because of a sterile environment. Something went wrong, the disease got loose, and it turns out that the re-written DNA horrifically kills people. Oops.

But a genius biochemist is probably not an idiot who decides to use an airborne vector for a genetic altering disease. Ahem. So he'll pick a better one, which is fluid-borne, inject it, and then keep his son in a sterile position. So, can this lead to an airborne contagious disease? Yes, but it's harder. This is where CRISPR takes over. Bacteria, you see, have a defense mechanism called CRISPR which is used to defend against foreign DNA - like viral DNA - and cuts it to pieces to stop it from working. Now, since it defends against viral DNA, CRISPR will take a sample of viral DNA so it know what to look for. Now what happens is that a bacteria is in the son and nabs a bit of the retrovirus's DNA for it's CRISPR. Not necessarily a bad thing. But then a weird mutation occurs - the bacteria starts ejecting CRISPR into it's otherwise unaffected host cell. And then the CRISPR goes and slices up human DNA - say the DNA responsible for creating certain essential proteins, like hemoglobin. And if this bacteria is an airborne bacteria, bad things happen. A bit farther fetched from an organic standpoint, but now we don't have an idiot biochemist.

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The "retrovirus" bit matters not at all. You can separate it completely from the transmission vector. "Retrovirus" is a property describing what a virus does within a cell. Transmission describes what it does outside.

As for viruses becoming airborne, the "how" is "it happened." "How" is a notoriously fickle concept when it comes to evolution. You typically can't find one. However, you may be very interested in Ebola Reston. Ebola is a highly virulent virus causing a lethal hemorrhagic fever. it's one of the nastier viruses in existence (You keep it in a Biohazard level 4 facility. For comparison, HIV can be processed in a level 2 facility). Reston is an airborne version of it. It mutated to become airborne in a small compartment of monkeys in Reston. I say that we typically can't find hows or whys with these evolving viruses -- in this case Reston was highly lethal to monkeys and not contagious within humans, and we have no reason "why" that was the case. it's simply what happened.

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Jaagsiekte sheep retrovirus (JSRV)

JSRV is an airborne retrovirus found in sheep which causes cancer. When JSRV creates a tumor large enough in the sheep's lungs, fluid generation increases and this fluid can then be expelled (coughing, breathing, panting) which spreads to other sheep in the area.

In other words, viruses spread through contact - what we mean when we say a virus is "airborne" is that it gets spread without physical touch of body parts (like STIs). So if you want an airborne retrovirus get it into fluid in the lungs. Viruses contained in the stomach will be spread through fecal matter; those contained in the genitals will be spread through genital contact; those contained in the lung tissue (and don't get expelled) are unlikely to spread except through surgery.

If your virus spreads into fluid in the lungs, it can be expelled simply through breathing, speaking, and coughing.

Seeing as we've already experimented with using manipulated forms of HIV/AIDS to treat leukemia, it wouldn't be far-fetched to see a doctor using what (he thought) was an inactive or manipulated form of JSRV to treat his dying child (perhaps JSRV activates certain enzymes which can reverse the negative effects of the child's illness). However, unbeknownst to him, this cures the illness but then either mutates or has unexpected negative consequences - and are now airborne.

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The child who is getting the cure happens to have also a flu.

The retro virus infects a flu infected cell.

The RNA is embedded into the viral genome, because we don't control where the insertion happens.

DOOM!

What was a common flu virus is now mutated.

Incidentally this is one of the mechanism by which every year we get a new flu virus. Different virus coinfecting the same host (suine, ducks, humans) and exchanging genetic code.

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