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As a preface, let me apologize to knowledgeable people if things I say make them wince, I have no genetics or virology background whatsoever and my science-speak is taken straight from Wikipedia.

The lore of my setting has a virus (man-made, neurological effects, near-100% fatality rate) wipe out most of humanity, and stay permanently present in the environment by becoming endemic to some animal species. However, I need this virus to have become virtually nonexistent for humans by the time my story starts, with the main goal of having let the world population bounce back a bit (not much, we're talking about Ancient Age levels, tops.)

For this purpose, I'm exploring the possibility of the virus' weakness being a rare gene, that would make it unable to survive in its host and quickly disappear before it's done any real damage. This gene would follow an autosomal dominant inheritance pattern, so that it eventually "takes over" completely as non-carriers die out while every carrier is guaranteed to pass it down to the next generation, effectively erradicating the virus among humans after some time and becoming the main reason they didn't actually go extinct.

Problem is that viruses mutate, quite fast, and I have no idea how much of a "fundamental" effect genes have over the ability of viruses to survive in a host — whether it could credibly be too much of an obstacle for mine to overcome, or if it'd just be like "aight" drop a new version of itself and finish the job. Any enlightenment on the matter would be appreciated.

As a plan B, if I'm allowed to ask a quick follow-up question: is there any technical reason that would have prevented the designers of the virus to purposefully make it unable to mutate?

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    $\begingroup$ Rather than using a virus, consider using a bacteria. Fewer mutations. More intereseting from an engineered perspective. The Bubonic Plague is a bacteria. They can be just as virulent and deadly - but unlike viruses, they don't require a living animal host to survive. Bacteria can be found proverbially hiding in caves until discovered by some poor schmuck who was just looking for a cool spelunking experience. And then declare that an inherited trait resists it and not worry about the specifics of how. $\endgroup$
    – JBH
    Jul 30 at 1:15
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    $\begingroup$ Extremely lethal viruses die out because they kill all their hosts. $\endgroup$
    – user458
    Jul 30 at 16:05
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    $\begingroup$ @Kubler A quick google review (google is your friend) suggests periods from days to weeks. But does it matter? It's an imaginary disease. Pick a number. Sometimes the effort to be as realistic as possible is simply wasted. It's not like there's a large group of PhDs waiting to read your story and judge whether or not it's "scientifically accurate." The goal of this site is to help you rationalize an imaginary world. You should be engineering the disease to meet the needs of your world and story, right? $\endgroup$
    – JBH
    Jul 30 at 18:11
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    $\begingroup$ I'm not sure if it is exactly the mechanism you describe, but if your requirement is a deliberately introduced highly lethal plague that wipes out most of the population, then sticks around without killing the last remnants, you could look into the introduction of the Myxoma virus to the Australian rabbit population. The resulting Myxomatosis disease was 99.8% lethal initially, before a combination of a resistant population (those 0.2% of the rabbits were the ones to breed) and mutations of the disease to be less lethal (as per Mary's answer), meant it didn't wipe out the rabbits. $\endgroup$
    – bificommander
    Jul 31 at 9:58
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    $\begingroup$ @bificommander Sounds like what I'm looking for, I'll do some research. Thanks! $\endgroup$
    – Kubler
    Jul 31 at 13:19

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Very credible.

The thing is that when a virus mutates, it does not stay the same in more than its specific vulnerability to a gene. It, for instance, becomes less lethal and less harmful. This is an advantage for it. It can spread farther because more people who catch it can have contact with other people rather than have to take to their beds, or die. It is very common for all diseases to grow less deadly even as the population that can contract it grows more resistant.

There are hypotheses that measles might have made the leap to a human disease (from rinderpest, a cattle disease) several times and burned itself out all but the last. Your disease can likewise remain in the animal population.

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    $\begingroup$ As answered, it's not even plausible, it's the norm. If lethal virii or viruses didn't burn out, then we'd all have been dead millions of years ago. $\endgroup$
    – Escoce
    Jul 30 at 2:25
  • $\begingroup$ However I'd caution against adopting the "Andromeda Strain" logical flaw, where all the organisms mutated in lockstep (i.e. at the same time, with the same mutation) rather than at random. $\endgroup$
    – Mark Morgan Lloyd
    Jul 31 at 17:13
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I have no idea how much of a "fundamental" effect genes have over the ability of viruses to survive in a host

Obviously that depends on the gene, but there's no reason they can't have a completely fundamental impact on how the virus functions. The classic example is malaria, which infects blood cells. If you have one copy of the sickle-cell gene, it modifies your blood cells such that the virus can't infect them. (If you have two copies, you get anemia, so it's not all roses. There's often a trade-off involved in biology.) In theory the virus could mutate to get around this, but at that point it would be a totally different virus with a different method of action.

is there any technical reason that would have prevented the designers of the virus to purposefully make it unable to mutate?

Yes. Mutating isn't something viruses intend to do, it's a side effect of the limited fidelity of protein replication. Every living thing makes these transcription and replication errors when creating new proteins, but they have enzymes whose job it is to police the output and break down any proteins that don't look right. Viruses don't have that extra protection, and may even have to bypass it.

(As an aside, there are certain organisms, bacteria mainly, that can deliberately shut off this machinery when under stress; they increase their rate of mutation "on purpose" as a way of potentially striking on something to overcome the stressor.)

You can try to provide some protection against your engineered virus mutating by making sure that common mutations in or near its active areas lead to a non-viable virus. (It's more accurate to say that it will still mutate, but those mutations won't have a chance to spread before they die out.) However, there's a practical limit to how much you can do this, and there's always the chance of multiple mutations arising at once and canceling out the intended killswitch, or a mutation in a part of the virus that wasn't active but is now, or what have you. Viruses are complex little beasts, and it's not always possible to predict what they'll do.

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    $\begingroup$ And when an organism is infected by two viruses at the same time, it can be the spot where the two viruses trade features. This may be how pigs mutate bird influenzas into a version that can infect humans. $\endgroup$
    – David R
    Jul 30 at 14:07
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Do the opposite. Virus is so deadly because it uses some cellular mechanism or some sort of protein. It cannot do any damage if the person lacks that particular gene. This way, the dealiness of the virus is tied to that particular gene and it cannot reasonably mutate while still being that deadly. It can survive in animals that have weakened immunity and animals will be fine as they lack the gene completely.

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This has already happened IRL

Genetic encoding have a way to defend against these viruses. An organism may develop a epigenetic lock on the viral DNA (after transpilation from its RNA, if necessary), making it inert.

Epigenetic mechanisms regulate all biological processes from conception to death, including genome reprogramming during early embryogenesis and gametogenesis, cell differentiation and maintenance of a committed lineage. ref

Since further infections would need to use the same loci, the organism with such epigenetic lock becomes immune to the virus. Also, mutations in the viral code may render it inert. It's DNA, so it is not immune to mutation.

Human DNA have a lot of viral code that is dormant or mutated into oblivion.

Eight percent of our DNA consists of remnants of ancient viruses, and another 40 percent is made up of repetitive strings of genetic letters that is also thought to have a viral origin. ref

Your virus has infected the population and killed a lot. Ancient humans on Earth suffered it several times. Then the virus code was deactivated by either epigenetics or mutation. The virus cannot infect the immune population, and becomes extinct. It becomes integrated to the creature's genome but serves no purpose.

Many bacterial and animal viruses lie dormant in the infected cell, and their DNA may be integrated into the DNA of the host cell chromosome. The integrated viral DNA replicates as the cell genome replicates; after cell division, the integrated viral DNA is duplicated and usually distributed equally to the two cells that result. ref

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