SF writer trying to get facts straight

[writerchick]

Hi everyone,

 

I'm working on a science fiction novel, and came here to hopefully get some help with Real Science in order to make my story more plausible. I love science, but I'm more of an occasionally-informed lay person than a serious student of the sciences.

 

My current story is about a human subspecies genetically engineered for immunity to a virus I call The Grip. Their immune systems create Grip antibodies, but humans' do not, and the Grip virus attacks the organs.

 

I have a ton of questions about viruses and immunity, and hope you can help. I'll start off with just a few:

 

1. If the virus appeared to the human immune system as a beneficial protein, would this explain why no vaccine would work on them? (Is there another easy explanation for why a vaccine is ineffective?)

2. If the subspecies created antibodies, and those were extracted and injected into an infected human, would they find and kill the virus? What sorts of reasons could I use to keep that from happening?

3. Is it more feasible to have a virus release a toxin that is deadly, or to simply kill healthy cells? Which would be more difficult to treat?

 

Thanks in advance for any help you can give me!

[GDG]

Hi everyone,

 

My current story is about a human subspecies genetically engineered for immunity to a virus I call The Grip. Their immune systems create Grip antibodies, but humans' do not, and the Grip virus attacks the organs.

 

I have a ton of questions about viruses and immunity, and hope you can help. I'll start off with just a few:

 

1. If the virus appeared to the human immune system as a beneficial protein, would this explain why no vaccine would work on them? (Is there another easy explanation for why a vaccine is ineffective?)

 

The immune system doesn't distinguish between beneficial and otherwise, but between "self" and "non-self" (and sometimes not even then, as in the case of auto-immune disease). Your virus would have to have more than one protein, but it is conceivable that its outer coat protein could resemble a normal human protein (e.g., serum albumin). Also possible that it could simply bind to a common serum protein, effectively cloaking itself in host proteins. However, the antibody system is more effective against bacteria and larger intruders: viruses are also (perhaps mainly) attacked by cell-mediated immunity (killer T cells, natural killer cells, etc.).

 

2. If the subspecies created antibodies, and those were extracted and injected into an infected human, would they find and kill the virus? What sorts of reasons could I use to keep that from happening?

 

Yep, if the antibodies were effective, that would work: it is called "passive immunity". When you get a poisonous snakebite, the antidote is antisera (antibodies) collected from horses. However, because the antisera is made up of foreign (horse) proteins, you can have a reaction to the antisera the next time it is administered (at least several weeks later): this is called "serum sickness". You would expect the subspecies to have the same antibody proteins, though, so unless you had some compelling reason for their antibodies to be mutated this would not be a plausible obstacle.

 

Most viruses enter the host cell by binding to a particular protein that sits on the outer surface of the cell. The specificity for that protein is part of what determines which species a given virus will infect, and what tissues in the body will be affected. For example, if your virus targets a protein that is only expressed on liver cells, you have a form of hepatitis. If your subspecies has a different form (e.g., a mutated version) of the key host protein, then their cells would not be infected. This is why people who have a mutation in CCR5 (a cytokine receptor) seem to be immune from HIV, as CCR5 is the primary route that HIV uses to gain access. (Unfortunately, HIV can also use a second receptor.)

 

3. Is it more feasible to have a virus release a toxin that is deadly, or to simply kill healthy cells? Which would be more difficult to treat?

 

Toxin release is more of a bacterial ploy, but it would not be impossible for a virus to encode a toxin. Antibodies can be used against toxins too. Toxin release could be a way of obtaining effects in the host other than those caused by the infection of particular tissues. However, keep in mind that most successful viruses are "successful" because their symptoms lead to spread of the disease. E.g., flu and rhinovirus make you sneeze, releasing an infectious mist.

 

BTW, "grippe" was an old name for a disease -- flu, if I remember right.

 

Best of luck with the story

 

Grant

[Mr Skeptic]

1. If the virus appeared to the human immune system as a beneficial protein, would this explain why no vaccine would work on them? (Is there another easy explanation for why a vaccine is ineffective?)

 

That is not necessary. A virus simply needs to not be recognized as foreign by the immune system. Some viruses mutate rapidly, so that even when the immune system recognizes one of the strains, a different strain may go unrecognized. Some viruses attack the immune system, effectively crippling any counter-attack. All viruses require a specific host protein to attack, and this generally makes viruses quite species specific. HIV does all of the above, so you may want to read up on it.

 

2. If the subspecies created antibodies, and those were extracted and injected into an infected human, would they find and kill the virus? What sorts of reasons could I use to keep that from happening?

 

As above, the virus could mutate rapidly into different strains so that an antibody against one strain would not affect all strains, and people can be affected with multiple strains at once. Hence, an antibody for each strain (there can be thousands in one individual in the case of HIV)

 

3. Is it more feasible to have a virus release a toxin that is deadly, or to simply kill healthy cells? Which would be more difficult to treat?

 

Viruses often kill cells as a side effect: the virus hijacks a cell to make multiple copies of itself, and often the way it leaves the cell is by lysing the cell open. A virus can produce toxins, which would make the virus more deadly but would also make it less contagious (due to killing the host before making as many copies as possible).

[Mokele]

1. If the virus appeared to the human immune system as a beneficial protein, would this explain why no vaccine would work on them? (Is there another easy explanation for why a vaccine is ineffective?)

 

I don't think any virus could do that, other than by hiding inside the body's own cells, which would hide it from anyone, human or superhuman.

 

If the subspecies created antibodies, and those were extracted and injected into an infected human, would they find and kill the virus? What sorts of reasons could I use to keep that from happening?

 

Yes, that's how snake anti-venom works. However, just like with anti-venom, there's a possibility of an allergic reaction.

 

Is it more feasible to have a virus release a toxin that is deadly, or to simply kill healthy cells? Which would be more difficult to treat?

 

The latter is much more within the purview of what a virus actually *does*. The former is more like a endotoxic bacteria.

 

Mokele

[writerchick]

Thanks so much for your replies!

 

The specificity for that protein is part of what determines which species a given virus will infect, and what tissues in the body will be affected. For example, if your virus targets a protein that is only expressed on liver cells, you have a form of hepatitis. If your subspecies has a different form (e.g., a mutated version) of the key host protein, then their cells would not be infected.

 

I think this was the info I was looking for! I was sort of thinking along the lines of canine parvo virus and how deadly it is for dogs but not at all for humans.

 

HIV does all of the above, so you may want to read up on it.

 

I will definitely do that next. I may have more questions afterward, I hope you don't mind. Thanks again!

[GDG]

"Subspecies" is an interesting choice of terms. I immediately get the sense that these people will be a persecuted group.

 

For most proteins in the body, you're going to have at least a few individuals (if not whole populations) where the protein is already mutated (like those few people who have a different form of CCR5, and thus appear resistant to AIDS). Unless the protein you pick is highly conserved (for example, its function is absolutely essential, and loss of function leads to death), there will be pre-existing members of your subspecies.

 

Not all viruses mutate rapidly: that is a characteristic of retroviruses, which have an RNA genome that gets copied (reverse-transcribed) into DNA after it enters the host cell. The virus reverse transcriptase is fairly sloppy, so errors (mutations) get written into the DNA copies, and multiple strains arise. Most other types of virus mutate (evolve) more slowly, although there are some (like influenza) that also reassort their proteins between different strains easily, which is why we have annual flu waves, and a new flu vaccine every year.

[writerchick]

Oh I see. Does that mean the faster a virus mutates, the more difficult it is to create a vaccine for?

 

If some viruses attack the liver, and some attack the T-helper cells, and some attack the respiratory system, is it feasible that one super virus could start out attacking one organ, then mutate in the body and attack something else?

[GDG]

Hmm, possible... With most non-retroviruses, you really don't expect to see radical mutation within the same host. The flu that you catch from your kids is the same flu that you pass on to your co-workers, etc...

 

Again, possible, but would take some real digging to find a situation that would be plausible. Here's a rough sketch of what happens in infection:

 

1. Virus enters the host: most frequently, through inhalation, but also through ingestion, sexual transmission, or by contact with a wound (the skin is otherwise a pretty good protection against viruses)
   
2. Virus latches onto host cell: typically, some part of the virus capsid specifically binds to a target protein or carbohydrate found on the outer membrane of the target cell.
   
3. Virus enters host cell: sometimes, just attaching to the host cell protein causes it to be internalized, along with the attached virus. In some, like HIV, attachment leads to fusion of the virus membrane with the host cell membrane, and release of the virus contents into the host cell.
   
4. Virus hijacks host cell: this varies from virus to virus. Retroviruses are reverse transcribed into DNA, which inserts into the host genome, and then gets transcribed and expressed as if it were host proteins. Other viruses are directly translated by host ribosomes (for RNA viruses), or transcribed and then translated (for DNA viruses). The virus typically also has a protein or two that suppress antiviral measures, and shut down or minimize the cell's normal transcription and translation of its own proteins. At this stage, the host cell will also take fragments of the viral proteins, stick them into MHC proteins, and present the MHC+viral fragment on the host cell surface. MHC ("major histocompatability complex") proteins are proteins that your immune system recognizes: when a lymphocyte encounters an MHC protein with a foreign protein stuck in its binding site, this signals the immune system that there is an infection, and T cells that can recognize that MHC+viral fragment develop. These cells become cytotoxic T lymphocytes (Tc cells), and go around destroying cells that are displaying that MHC+viral fragment on their surfaces.
   
5. Virus replicates: the virus, using the host cell's machinery, makes multiple copies of itself.
   
6. Virus escapes: the virus may bud out through the host cell membrane, or it may simply keep replicating until the cell bursts open, releasing all of the virus particles inside. Your immune system tries to kill off the infected cells before they can be used to make more virus particles. The infection becomes an arms race, between viruses replicating as fast as they can, and the immune system trying to mature more Tc cells and B cells (making antibodies) as fast as it can. (Incidentally, this is why we have vaccines: once the immune system has been exposed to a pathogen, it is usually much faster to come up to speed the second time it encounters that pathogen.)
   
7. Virus is transmitted: the virus must pass on to the next host, or you won't have a chain of infection, and the virus will die with your host. Basically, the virus needs to end up packaged in something that will encounter another host, most commonly a biological fluid like blood, mucus, saliva, etc. Back to Step 1.
   

 

The immune system exerts a selection pressure (think evolution) on the population of viruses. If a virus mutates in such a way that the Tc cells no longer recognize it, then it escapes from surveilance for a while. However, most mutations either (a) do not affect a part of the protein that the Tc cells were using for recognition, or (b) adversely affect the virus's ability to replicate or infect. For example, if the virus capsid protein is mutated so that it no longer binds to the host target protein, the virus can no longer enter the cell, and just gets taken out with the trash. Viruses with impaired replication get out-competed by unimpaired viruses, and by the host immune system.

 

For a virus to mutate from one tissue specificity to another would require that the target proteins be pretty similar, but different, so that altering the virus capsid protein by only one or two amino acids would cause it to bind more strongly to one host protein over the other. Possible, but not very likely. It is possible, however, that the virus encodes several different capsid proteins (or, better, assembles the capsid sequence out of several parts that can be mixed and matched -- this is how your body makes so many different antibodies), and under pressure from the immune system would switch to a different capsid protein. The malaria parasite does something like that to evade the immune system (although, remember, the malaria parasite is many, many times larger than a virus).

 

OK, that's a rough overview. There is a lot more detail, but this is probably already more than you want to read Your local library probably has a few good textbooks on immunology, which would be worth a read to really familiarize yourself with the subject. All part of the background research for a good scifi story

 

Best of luck,

 

Grant

[writerchick]

Thank you so much! I'm still trying to get my head around all that.

[writerchick]

If I understand correctly, viruses are attracted to cells with a particular type of protein on their surfaces. Is there such a thing as a "free floating" protein, or a protein that's part of something else that isn't a living cell, but that could fool a virus particle into attaching to it? Sort of like a magnet? Maybe the virus would be rendered inert because there's nothing inside the host to let the virus reproduce?

[Mokele]

That's actually what antibodies do - they flow freely through the bloodstream, binding to any viri they find, labeling them as something to be destroyed by the rest of the immune system.

[writerchick]

How about in a person without the ability to create antibodies? I read this (very interesting) article about a protein found in deer tick saliva that keeps the HIV virus from latching onto T cells. I wondered how such a protein would be introduced into a person with HIV in order to stop it from reproducing further.

[GDG]

How about in a person without the ability to create antibodies? I read this (very interesting) article about a protein found in deer tick saliva that keeps the HIV virus from latching onto T cells. I wondered how such a protein would be introduced into a person with HIV in order to stop it from reproducing further.

 

Sure, your blood contains a number of proteins other than antibodies (e.g., serum albumin, complement factors, etc.). One way of thwarting your virus would be to introduce solubilized receptors, i.e., clone the protein that your virus recognizes, and truncate off the membrane anchor (assuming it has that morphology). Free floating, unattached receptors would soak up a bunch of the virus: if present in concentrations much higher than the native (real) receptor, it might successfully stop the infection. Of course, it would also compete for the natural ligand of the native receptor, which could cause other side effects.

 

The protein could be introduced by IV, or by gene therapy (the latter works mainly in science fiction right now ).

 

Grant

[throng]

Hi everyone,

 

I'm working on a science fiction novel, and came here to hopefully get some help with Real Science in order to make my story more plausible. I love science, but I'm more of an occasionally-informed lay person than a serious student of the sciences.

 

 

 

 

 

My current story is about a human subspecies genetically engineered for immunity to a virus I call The Grip. Their immune systems create Grip antibodies, but humans' do not, and the Grip virus attacks the organs.

 

I have a ton of questions about viruses and immunity, and hope you can help. I'll start off with just a few:

 

1. If the virus appeared to the human immune system as a beneficial protein, would this explain why no vaccine would work on them? (Is there another easy explanation for why a vaccine is ineffective?)

2. If the subspecies created antibodies, and those were extracted and injected into an infected human, would they find and kill the virus? What sorts of reasons could I use to keep that from happening?

3. Is it more feasible to have a virus release a toxin that is deadly, or to simply kill healthy cells? Which would be more difficult to treat?

 

Thanks in advance for any help you can give me!

 

 

A virus is basically a tiny bundle of genetic material—either DNA or RNA—carried in a shell called the viral coat, or capsid, which is made up of bits of protein called capsomeres. Some viruses have an additional layer around this coat called an envelope. That's basically all there is to viruses.

 

Some viruses insert their genetic material into the host cell’s DNA, where they begin directing the copying of their genes or simply lie dormant for years or a lifetime. Either way, the host cell does all the actual work: the viruses simply provide the instructions.

 

Viruses can also influence host genes by where they insert themselves into their host’s DNA. Recent decoding of the human genome shows that viral DNA sequences have been reproducing jointly with our genes for ages.

 

The viral genes are then copied many, many times, using the machinery the host cell would normally use to reproduce its own DNA.

 

http://www.microbeworld.org/microbes/virus/

 

 

"DNA, the molecule that contains the script of life, encodes its data in a four-letter alphabet. This would be an ideal medium for storing a cosmic calling card. In many organisms, humans included, genes make up only a tiny fraction of their DNA. Much of the rest seems to be biological gobbledygook, often called "junk DNA". There is plenty of room there for ET to etch a molecular message without damaging any vital genetic functions. See:

 

much of human DNA consisted of what has been called "junk" DNA. Junk DNA is DNA that does not make up genes - and so does not serve any functional

 

purpose.over time humans had incorporated DNA into the genome which was not human in origin,

 

The junk DNA resembles transposable elements - pieces of DNA that move around and insert themselves into other stretches of DNA - in the way that viruses do. So it has been thought by some that in the past humans contracted certain viruses and the virus sequences became a part of human DNA, being passed on from generation to generation in an inactive state." Paul Davies phd

[writerchick]

"... and the virus sequences became a part of human DNA, being passed on from generation to generation in an inactive state."[/i]

... just waiting for a SF writer to come along and take advantage!

 

Thanks a bunch! That was very intriguing!

[GDG]

The idea that the genome is full of "junk" DNA that serves no purpose is becoming more and more suspect. It appears likely that much (if not most) of the "junk" DNA actually encodes short interfering RNAs (iRNA), long non-coding RNA (ncRNA) and others that are now considered important regulatory factors. (See, e.g., T.R. Mercer et al., Nature Rev Genetics (2009) 10:155-59, "Long non-coding RNAs: insights into functions".) In other words, DNA encodes things besides just protein. The fact that we don't know exactly what all of it does doesn't mean that it does nothing. Evolution tends to pare that stuff away...

 

True, there are genomic fossils left by retroviruses in our ancestry (see, e.g., A. Ruggieri et al., Retrovirology (2009) 6:17 [free article]). Sometimes, the retroviral proteins are taken up and used by the host for other purposes: examples include placental morphogenesis, tissue specificity of enzyme expression, and host defenses, as well as using retroviral promoters and splicing sites for other proteins. (For a list of references, see M.V. Eiden, Cell Mol Life Sci (2008) 65:3327-28.)

 

Enjoy,

 

Grant

[CharonY]

EEeeeek Paul Davies.....

[writerchick]

Is there any chance that there's some as-yet-unidentified coding RNA as well? Or is all the coding stuff identified already? (Sorry, I'm kind of a genetics noob too!)

[CharonY]

Only a limited number of coding gene regions (and their products) have been identified to date. The current available numbers of genes in humans for instance, is based on estimations, not on actually having identified all of them.

[GDG]

Is there any chance that there's some as-yet-unidentified coding RNA as well?

 

Guaranteed

[writerchick]

I was just reading the definition of an enzyme: "A protein molecule produced by living organisms that catalyzes chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions."

 

and "a protein made in the body and capable of changing a substance from one form to another"

 

So can an enzyme change the nature of a virus, such as make it not attack the cells it used to target?

[Mokele]

It could bind to the site the virus uses to gain entry into the cell.

 

More directly, a digestive enzyme could attack the protein coat of the virus, breaking it down and destroying it, but it would also wind up attacking anything else it bumped into.

[Mr Skeptic]

So can an enzyme change the nature of a virus, such as make it not attack the cells it used to target?

 

Yes, in theory. But that is not how our immune system works. The reason is, an enzyme is extremely specific yet hard to evolve, so you would need a different enzyme for each virus, and even for each strain of virus. More likely, for immunity you just have some people with a different configuration of the protein that the virus targets, and this is incidental rather than specifically intended to fight the disease. Remember, viruses are not at all clever (most don't consider them alive) -- they require you to have a vulnerability to it to attack you, in addition to the much easier task of slipping by your immune system.

[GDG]

So can an enzyme change the nature of a virus, such as make it not attack the cells it used to target?

 

Sure, this is possible, although I don't know of any examples. Some enzymes are proteases, which means that they cleave a protein into smaller bits. Most proteases are specific for a particular amino acid sequence, meaning that they will only cut certain target proteins, and only at a particular place in the protein sequence. There are many examples of proteins that are expressed in an inactive form, which become active only after a protease removes part of the protein. For example, insulin is expressed as a single amino acid chain, which is inactive. A protease clips out a section of the middle of the sequence, leaving the two ends bound together: that is the active form. In some cases, the protein that gets activated is itself a protease, which goes on to activate still other proteases, and so on. The coagulation system and the complement system are two other examples. You should really read up on biology -- it is fascinatingly complex.

 

So it is conceivable that your subspecies (or uberspecies) could have an enzyme that hydrolyzed (cut) part of the grip virus capsid, and thereby prevented it from binding to cells. Of course, as soon as this fact was recognized, that enzyme would become the cure: pharmaceutical companies would simply manufacture the enzyme, for intravenous injection. Instant cure. You'd have to set it up so that the subspecies enzyme also cleaved an essential "normal human" protein, so that it would be unusable for the rest of the population. Perhaps it would activate the clotting cascade, so that a normal human's entire circulatory system would clot up instantly upon administration Could be a good plot development point

[Mr Skeptic]

I take that back. RNAses are enzymes that digest RNA, and they attack all RNA viruses, to some extent anyways.