Viruses Viable For Genetic Modification

Alsikepike · May 4, 2017

I'm writing a story about a group of test subjects being given superhuman abilities through use of genetic modification. The way this works is that scientists have modified a virus to carry the specific genes they want to introduce to the test subjects. Viruses are already used for gene therapy in a similar way, so I'm well within the realm of realism. What I need from you guys is a virus that can be used as a catalyst for this kind of task. Does anybody know of a virus that fits the criteria I have below? I know I could just say, "a genetically modified virus," and no one would bat an eye, but I'd like the process to have ties to the real world by using a real world virus.

The requirements for the virus are:

Relatively recognizable
Not airborne, and generally not super contagious (Obviously it wouldn't be good for a genetically modified virus infecting anything it shouldn't. We've all seen movies, we know how that goes)
Capable of infecting a range of different cells (There are some viruses that are cell-specific)

I do have some preferences for the virus too, but these are generally things that aren't completely necessary to the story, as the whole,"genetically modified," thing can cover for any extra features of the virus pretty easily.

My preferences are:

A relatively large virus (The main limitation for this kind of genetic modification is the amount of genes you can fit into it and still have it work)
Something that can affect muscles, joints, bones, or nerves. (Any of the four will do)
A relatively simple structure
Uses RNA instead of DNA (RNA viruses are more likely to end up in a cell's genetic code)
Something that doesn't kill cells when it reproduces (REALLY not an issue if this is left out, as minor regeneration of tissues will be one of the abilities aquired anyway)

I've already had a few ideas, the first is the poliovirus, (infection vectors can be managed in a controlled environment, already used for genetic modification, affects nerves and muscles, uses RNA, and very simple) and the other was the Rabies virus (relatively difficult to accidentally be infected in a controlled environment, larger than the polio virus, also affects muscles and nerves, uses RNA, and doesn't kill infected cells) these are the prime candidates so far. If you can't think of a virus that meets the criteria above, providing your opinion on these two viruses would still be of great help to me.

Now before you say it, I am aware that there is a completely harmless virus already used for genetic modification (the name escapes me at the moment), so don't tell me I'm over-complicating things. (Not for that, anyway. I'm well-aware I don't need to be this specific) I'd rather use a more identifiable virus because I'm trying to build a theme with humans hijacking nature's tools because humanity struggles to do what nature does so, well, naturally.

Basically, does anybody know a virus that at least fits the first three criteria?

MaeZe · May 4, 2017

Could you summarize your question?

Alsikepike · May 4, 2017

Yeah, I'm sorry. I kinda rambled on there, didn't I? My question is, do you know a virus that fits the criteria I provided? I'm gonna edit that post down. The last post I made is mostly filled with replies telling me why the scenario I provided for the question I had was unlikely, rather than actually answering my question. I guess I overcorrected by trying to prove my scenario for this post is accurate.

Cyia · May 4, 2017

The DNA isn't integrated. The virus has its genetic material removed and replaced with whatever the gene therapy's wanting to pass on, leaving the viral shell as little more than an injection system. It would be more like taking the insulin out of a hypodermic, sanitizing the inside, and then refilling it with atropine.

And if you alter the RNA, then it alters the DNA. One is used to copy the other. Maybe if you can come up with something that alters or fractures the Uracil in the RNA, which would then alter the Thymine in the DNA, you could make it work. That way the DNA would seem normal until replication, where the Uracil is coded incorrectly, or else it forces the incorrect replication of the Adenine-Thymine base pairs.

You might look into T-4 or even T-7, which is used to alter bacteria. You might be able to hand-wave something with that, using an altered bacteria to infect otherwise healthy people.

A synthetic virus is a good idea, too.

Alsikepike · May 4, 2017

I know that viruses don't do that for gene therapy, I was just trying to associate the process as being of a similar concept. The process I have in mind is more permanent. But I'll look into the T-4 and T-7 bacteriophages. I'm okay with a synthetic virus, but how it infects an organism depends on the type of ,"needle," you use, so I'd at least like it to be based on something.

Alsikepike · May 4, 2017

I'm not planning to go into too much detail. It was supposed to be just a thing for the virus to have originated from, basically just a name. Something that you can read and realize, "Hey this is actually rooted in the real world." Kinda like how Jurassic Park actually explained the science behind how people were able to bring dinosaurs back from extinction. Extracting DNA from dinosaur blood found in ancient mosquitoes. Not super complicated, just something to make you think.

MaeZe · May 4, 2017

Alsikepike said:
Yeah, I'm sorry. I kinda rambled on there, didn't I? My question is, do you know a virus that fits the criteria I provided? I'm gonna edit that post down. The last post I made is mostly filled with replies telling me why the scenario I provided for the question I had was unlikely, rather than actually answering my question. I guess I overcorrected by trying to prove my scenario for this post is accurate.

You're asking us to discuss virus vectors like you'd ask someone to suggest the best flavored apples in our experience. My specialty is infectious disease and I couldn't name any virus that fits your criteria. I would say steer clear of pathogens. And who knows the names of any viruses that aren't pathogens?

As for polioviruses not being very contagious, that's wrong. They are extremely contagious. It's just that 95% of people infected don't develop neurological symptoms.

I don't know of a single virus that isn't cell specific. They have to match cell wall receptors in order to enter the cell.

As for DNA vs RNA, I think you might want to review that one. Our Inner Viruses: Forty Million Years In the Making

Scientists know this melding has happened because viruses have distinctive genes. When scientists scan the human genome, they sometimes come across a stretch of DNA that bears the hallmarks of viruses. The easiest type of virus to recognize are retroviruses, a group that includes HIV. Retroviruses make copies of themselves by infecting cells and then using an enzyme to insert their genes into their host cell’s DNA. The cell then reads the inserted DNA and makes new molecules that assemble into new viruses.

Most of the time, retroviruses behave like other viruses, jumping from host to host. But sometimes a retrovirus will end up in the genome of an egg or sperm. If it then ends up in a new embryo, the embryo will carry a copy of the virus in every single cell–including its own egg or sperm. And on and on, from parents to children to grandchildren....

We carry about 100,000 pieces of DNA that came from retroviruses–known as endogenous retroviruses...

Retrovirus

A retrovirus is a single-stranded positive-sense RNA virus with a DNA intermediate and, as an obligate parasite, targets a host cell. Once inside the host cell cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards).

HSV, on the other hand, is a DNA virus that easily becomes part of the human cell. That's how one gets chicken pox as a kid and it erupts as shingles decades later.

You might be going about this the wrong way. Have you read the basics of the field like maybe starting with Viral vectors?

Alsikepike · May 4, 2017

Im sorry, I should've clarified. I forgot to edit the part with how infectious the poliovirus is. I meant to put the same thing as the rabies virus. It's transferred via the fecal-oral route, something much easier to control in a controlled environment. In terms of cell-specifics, the poliovirus is capable of infecting any cell that sports a CD155 receptor, which is just about any cell in the human body. But many cells sport interferons to deter viruses like polio. There's an experiment where mice were genetically modified to sport the CD155 receptor, but lack the interferons. The mice showed the poliovirus in a notably wider range of tissues. I'll send you the link if you want it, it's an interesting read. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951287/ But I appreciate the criticism, I'll look into those links you provided, and I'll try to clarify more in the future.

MaeZe · May 4, 2017

Alsikepike said:
Im sorry, I should've clarified. I forgot to edit the part with how infectious the poliovirus is. I meant to put the same thing as the rabies virus. It's transferred via the fecal-oral route, something much easier to control in a controlled environment. In terms of cell-specifics, the poliovirus is capable of infecting any cell that sports a CD155 receptor, which is just about any cell in the human body. But many cells sport interferons to deter viruses like polio. There's an experiment where mice were genetically modified to sport the CD155 receptor, but lack the interferons. The mice showed the poliovirus in a notably wider range of tissues. I'll send you the link if you want it, it's an interesting read. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951287/ But I appreciate the criticism, I'll look into those links you provided, and I'll try to clarify more in the future.

I think you're misreading that article. It's not saying poliovirus can infect any human cell. That the CD155 gene is in humans and not in other animals doesn't mean every cell membrane has the glycoprotein.

The PV receptor is a transmembrane glycoprotein. All cell membranes have transmembrane glycoproteins. If they didn't then things could not get in and out of the cell. While it is a common transmembrane glycoprotein, all cell membranes don't have the PV receptor, at least not in a form the poliovirus can use.

CD155:The Poliovirus Receptor

Structure
CD155 has attained the name poliovirus receptor (PVR) in light of the fact that it is responsible for mediating the transmission of poliovirus through the cell membranes of host cells. ... Some variation on the location of CD155 in the cell has been found. As well as being bound in the cell membrane, CD155 has been found in an excreted form ... The membrane bound forms of CD155 have been termed PVR alpha and sigma. Those variations that do not contain a transmembrane domain are termed PVR beta and gamma. The importance of these distinctions in structure is that it appears that poliovirus can only bind to CD155 and infect the host cell if the protein is found in the transmembrane form.

So this particular glycoprotein is common and exists in locations other than the cell membrane. But if poliovirus receptors were on every cell membrane, the poliovirus would infect your lungs, cuts or other breaks in the skin, your eyes, and it's unlikely that 95% of the people infected would escape neurological involvement.

One hundred years of poliovirus pathogenesis is particularly informative re: poliovirus infecting the cell.

In humans, poliovirus has been isolated from tonsillopharyngeal tissue, the wall of the ileum, and mesenteric lymph nodes (Sabin and Ward, 1941). ...

Human epithelial cells produce high levels of CD155 RNA, suggesting that these cells might be primary sites of poliovirus replication (Ren, 1992). In humans, CD155 protein was detected on the intestinal epithelium, M cells of Peyer's patches, and in germinal centers within the Peyer's patches (Iwasaki et al., 2002). ...

Experimental findings in humans and monkeys subsequently proved that poliovirus does not invade the central nervous system by the olfactory route (Sabin and Ward, 1941)....

Although poliovirus is believed to be transmitted by fecal–oral contamination, in countries with high standards of hygiene, virus may be transmitted by the respiratory route. The source of virus for this mode of transmission is the tonsils and pharynx. Replication at these sites usually occurs after virus replication in the intestine and spread by viremia. When infection is spread by the respiratory route, it is not clear if virus replicates in the nasopharynx, or is ingested and replicates in the intestine....

CD155 has been detected at the neuromuscular junction of human muscle (Leon-Monzon et al., 1995).

That last bit about the respiratory route is really talking about droplet spread. It's in a persons mouth and throat, they cough and droplets make it into someone else's nose or mouth. It's still primarily a fecal oral spread virus.

But none of this is necessary. Your readers aren't going to care. You might want to have a biologist familiar with the subject matter review your book once it's written if you are concerned about technical accuracy.

I suggest you concentrate on literature on viral vectors and go from there. You don't need a perfect vector. We've been making designer viruses for years. Make your own from scratch.

Cath · May 5, 2017

I've deleted the posts suggesting the OP 'makes it up'. Please refer to the second post on the forum guidelines. Thank you.

Cyia · May 5, 2017

But synthetic viruses are a real thing. You can "make up" your own virus.

https://en.wikipedia.org/wiki/Synthetic_virology

You can also manufacture synthetic versions of existing viruses:

Including synthetic Polio: http://science.sciencemag.org/content/297/5583/1016

And synthetic bacteriophages: http://www.pnas.org/content/100/26/15440.full

This includes cloning sections of DNA to reassemble a virus in-lab. It also includes creating fully synthetic microbes to combat / resist said viruses. There's nothing preventing someone from creating their own virus from scratch to meet the needs of their situation.

King Neptune · May 5, 2017

There'[s a huge difference between synthesizing a virus and "making it up". Synrthetic viruses have already been made for working on this kind of procedure.
http://news.bbc.co.uk/2/hi/science/nature/2122619.stm
https://en.wikipedia.org/wiki/Synthetic_virology

This is a new field, and it hasn't been widely used, but synthetic viruses have advantages over natural ones in that one can make them act as one likes. Trying to find a natural virus that will function as the OP wishes might be imposssible, but it should be possible to synthesize one that would.

Cath · May 5, 2017

King Neptune, your post specifically says make it up OR say it was synthesized, so that argument isn't going to fly.

You also made assumptions about how the OP would use the information.

I'll refer you again to the second post in the forum guidelines:

Cath said:
I'm seeing a lot of replies that either:

Comment on the story rather than answering the question.

Suggest the OP 'makes it up' because no-one expects fiction to be true to life (especially if the OP is asking about Science Fiction or Fantasy).

This won't fly here. Posters should expect fact-based or experience-based responses. And this is NOT a place for brainstorming stories ideas without a fact-seeking element to the question, there's a whole other area of the forum for that.

Posts that suggest making up the facts to fit the story or otherwise commenting on the story rather than answering the question may either be punted to another forum or deleted entirely. You have been warned.

King Neptune · May 5, 2017

Cath said:
King Neptune, your post specifically says make it up OR say it was synthesized, so that argument isn't going to fly.

You also made assumptions about how the OP would use the information.

I'll refer you again to the second post in the forum guidelines:

That is to say that you know nothing about tailored viruses, not even in concept.
With the development of CRISPR, tailored micro-organisms are available to more university and research labs all the time. If you can't find what you want in nature, then alter it to more closely fit the specifications. It isn't possible to create any kind of DNA in a lab, but some people are thinking about the possibility of "enhanced" humans; do you want wings? This is new technolog, so the limits aren't known. For gene therapy the possibility is clear, redesign the gen so the defect isn't there.
https://en.wikipedia.org/wiki/CRISPR

Cath · May 5, 2017

This is your post.

Which virus you use is not important, or you could say that it was a synthesized virus developed just for this purpose. Going into too much detail about this will bore the non-scientists and give the scientists an opportunity to stop suspending disbelief.

It contains no information helpful to the OP. Stop pretending you were more helpful than you were.

Beanie5 · May 5, 2017

I think aids is the virus you are looking for and it could optionally introduce a weakness to your superpeople, if you were more specific about the abilities it might be easier to construct a delivery mechanism, what you are looking for is something perhaps introducing (injecting )a new chromosome ( unwrapped or blocked ) to be read in the target cells that then cancer like might produce another or super organ this might be compisite super oxygen absorbing lungs allowing room for a larger/stronger heart. ( it might take several viruses or an rna templte because i doubt a virus could carry a whole chromosome perhaps a mini chromosome.) resulting in both increase breathing and stamina ( the two compliment each other) You might need some stem cells somewhere as well

AW Admin · May 5, 2017

King Neptune said:
That is to say that you know nothing about tailored viruses, not even in concept.
With the development of CRISPR, tailored micro-organisms are available to more university and research labs all the time. If you can't find what you want in nature, then alter it to more closely fit the specifications. It isn't possible to create any kind of DNA in a lab, but some people are thinking about the possibility of "enhanced" humans; do you want wings? This is new technolog, so the limits aren't known. For gene therapy the possibility is clear, redesign the gen so the defect isn't there.
https://en.wikipedia.org/wiki/CRISPR

Right. You have had multiple polite requests from an exceedingly courteous mod, and you've chosen to ignore them.

Not ok.
Again.

Cyia · May 5, 2017

Beanie5 said:
I think aids is the virus you are looking for and it could optionally introduce a weakness to your superpeople, if you were more specific about the abilities it might be easier to construct a delivery mechanism, what you are looking for is something perhaps introducing (injecting )a new chromosome ( unwrapped or blocked ) to be read in the target cells that then cancer like might produce another or super organ this might be compisite super oxygen absorbing lungs allowing room for a larger/stronger heart. ( it might take several viruses or an rna templte because i doubt a virus could carry a whole chromosome perhaps a mini chromosome.) resulting in both increase breathing and stamina ( the two compliment each other) You might need some stem cells somewhere as well

Not a chromosome.

Species are defined by their chromosome count, which is in pairs. When you get a trisomy, you end up with conditions that range from Down-syndrome to catastrophic failure in development, so you don't want to go adding them randomly. Even just doubling a Y-Chromosome can impact development (several studies focus on the increased aggressiveness in death row inmates who are double-Y's)

But people with trisomy of an existing chromosome pair are still 100% human. They've still got 23 pairs of chromosomes with an unusual tripling of one. This isn't the same as inserting a wild card, singular chromosome in a lab or by exposure to some exotic virus. (I'd go so far as to say this is literally impossible for a *single* chromosome.)

Now, if you want to try and craft or force an allele that will pop dominant over an existing allele, that wouldn't have near the consequences of forcing an extra chromosome into the mix. The only way altering the number of chromosomes would work would be to introduce a full pair, *and* to qualify the resulting person as non-human by chromosome count.

Back to the OP, West Nile might give you the criteria you want. I just double checked and it is indeed an RNA virus. SARS could work, too, as it's highly virulent.

Beanie5 · May 5, 2017

Funnily enough I have wondered if down's syndrome was an evolutionary shot that ended poorly. Perhaps the subjects of the genetic experiment could suffer
from downs an the virus works on the (haploid not sure correct terminoligy here ) gene to unlock its true potential . This is beyond my knowledge i am afraid.(99.9% of mutations are bad but every so often, any one for lemarkian evolution i hear it is getting more legs all the time.)

Alsikepike · May 5, 2017

I think that's a good idea, and what's nice is that HIV also can stay dormant within cells for a long time, which works for another part of the story I'm planning. I'll look into it.

MaeZe · May 5, 2017

Alsikepike said:
I think that's a good idea, and what's nice is that HIV also can stay dormant within cells for a long time, which works for another part of the story I'm planning. I'll look into it.

HIV doesn't stay dormant.

Here are some differences using examples.

Tuberculosis (bacteria so it's just to illustrate) infects a person. If not killed outright or causing infection right away, living bacteria that are very slow growing are walled off by the immune system. There they can live and decades later break out of the walled off area to cause disease. We call that latent TB infection. It is not dormant.

Then there is the varicella virus. You get infected and develop chicken pox. That virus truly does become dormant in a nerve root. Years later it can recur as shingles. If we tested your blood, we would not find varicella virus while the virus was dormant.

The HSV 1 and 2 viruses are dormant in between being active. Sometimes though, there can be viral shedding without ulcers. The virus can transmit infection without symptoms.

Hepatitis B and C viruses, rather than being dormant typically are replicating in the liver cells and can be recovered from the blood stream if your body does not eliminate the virus during the initial infection. They are not dormant despite the fact liver disease may not be severe enough to notice symptoms until years of damage accumulate.

HIV, as we've known for years but it wasn't known back in the 80s and early 90s, is not dormant. In fact, without treatment, it replicates like crazy. But the immune system can tolerate it for an average of 5 years (there are some people this is shorter and in a few, much longer). At that time the immune cells just can't keep up and one's white cell counts begin to drop. That's where opportunistic infections begin to ravage the person.

Now, however, with careful drug treatment, viral replication can be kept low enough the immune system is spared. But you don't see viral loads going to zero.

There's a nice explanation here.

HIV lives inside one of your immune cells, the CD4 T cells. These cells can sleep in reservoirs around the body. HIV treatment only works on active cells and so cannot reach those cells that are ‘resting’ in the reservoir. These cells wake up sporadically and are the reason you always have some virus.

Your viral load is never zero. At very low levels measuring viral load is dependent on the sensitivity of the test itself. Most tests have a cut-off of 50 copies/mL.

In research studies using more sensitive tests, about 50% of peope undetectable to less than 50 are also undetectable on a test sensitive down to less than 5 copies/mL. Many of these people are undetectable on a test sensitive to 1 copy/mL but they with still have virus somewhere,

The genital tract, the brain and CSF, the lymph nodes are other areas where HIV levels can be higher, but these are difficult areas to test.

Viral load below 50 the viral load is probably bliping up and down below 50 or even below 5 rather than being stabilised at a fixed level.

Viral load above 50 appears to be the cut-off value, above which there is a possibility resistance can occur. This is why the aim of less than 50 is set.

BTW, HIV would be a very bad choice, in my opinion. One reason is viruses vary in how stable they are. Like influenza, the HIV virus is not stable and constantly mutates. You need a viral vector that is a more stable molecule.

MaeZe · May 5, 2017

Beanie5 said:
Funnily enough I have wondered if down's syndrome was an evolutionary shot that ended poorly. Perhaps the subjects of the genetic experiment could suffer
from downs an the virus works on the (haploid not sure correct terminoligy here ) gene to unlock its true potential . This is beyond my knowledge i am afraid.(99.9% of mutations are bad but every so often, any one for lemarkian evolution i hear it is getting more legs all the time.)

For the record, Down's syndrome results from defective chromosome division when the cell divides. Evolutionary changes typically occur at the nucleotide level, not with whole chromosome damage.

And most mutations in the genome are harmless, neither good nor bad. There's a lot of leeway in the system.

Viruses Viable For Genetic Modification

Alsikepike

MaeZe

Alsikepike

Cyia

Rewriting My Destiny

Alsikepike

Alsikepike

MaeZe

Alsikepike

MaeZe

Cath

The mean one

Cyia

Rewriting My Destiny

King Neptune

Cath

The mean one

King Neptune

Cath

The mean one

Beanie5

Live a poem...Or die a fool. \/

AW Admin

Cyia

Rewriting My Destiny

Beanie5

Live a poem...Or die a fool. \/

Alsikepike

MaeZe

MaeZe