Endogenous Retroviruses II

[NewCreature]

Which entity will collect more mutations during a given timespan, ERV's or the sequence of retroviral DNA within a retroviral "population"?

Each viral particle is formed with a likely error (mutation), but it is deaf to the mutations of all the other virions in the population. So we end up with a release of many virions all with unique mutations, but with no ability for all the mutations to accumulate since they were all transcribed from the same pattern. Many ERVs suggest that they have translocated, mutated, and deleted. Some have up to 2000 instances of location.

Isn't the retroviral population simply a function of the proviral integration? The gratest way to change the virus is by changing the proviral sequence that codes for the virus. Once the proviral sequence is no longer capable of producing virions it is the only thing left changing. Perhaps the single biggest factor in viral immunity is the bodies ability to mutate the proviral integration through many of the involved mechanisms to the point that it cannot produce infectious particles. I guess I don't see what your point is.

In the case of ERVs the genetic structure is no longer coding for retrovirus. Many erv's don't show exogenous examples. So as a funtion of time I would say that the ERV's collect more mutations since the are all that is changing. That's a little like saying which grows faster a tree or nothing.

[BGoodForGoodSake]

Which entity will collect more mutations during a given timespan, ERV's or the sequence of retroviral DNA within a retroviral "population"?

Each viral particle is formed with a likely error (mutation), but it is deaf to the mutations of all the other virions in the population. So we end up with a release of many virions all with unique mutations, but with no ability for all the mutations to accumulate since they were all transcribed from the same pattern. Many ERVs suggest that they have translocated, mutated, and deleted. Some have up to 2000 instances of location.

OK, I can see where you got confused. What I meant will be clarified below.

Isn't the retroviral population simply a function of the proviral integration? The gratest way to change the virus is by changing the proviral sequence that codes for the virus. Once the proviral sequence is no longer capable of producing virions it is the only thing left changing. Perhaps the single biggest factor in viral immunity is the bodies ability to mutate the proviral integration through many of the involved mechanisms to the point that it cannot produce infectious particles. I guess I don't see what your point is.

In the case of ERVs the genetic structure of the orignial retrovirus is no longer changing. Many erv's don't show exogenous examples. So as a funtion of time I would say that the ERV's collect more mutations. That's a little like saying which grows faster a tree or nothing.

I don't agree with this statement at all. What does the absence of exogenous material have to do with mutation rates? This is a rhetorical question.

Here is the crux of the issue. Retroviral material must pass from host to host and in the process the viral material changes. The question then is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse?

Endogenous material being the result of integration of viral material into a germ cell.

[NewCreature]

What does the absence of exogenous material have to do with mutation rates? This is a rhetorical question.

Here is the crux of the issue. Retroviral material must pass from host to host and in the process the viral material changes. The question then is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse?

Endogenous material being the result of integration of viral material into a germ cell.

OK I realize it is rhetorical, but I feel it is an important question. In the abscense of an exogenous living population of an ERV all that is left changing is the ERV. When the ERV mutated enough it could no longer code for the virus and the viral population stopped mutating. The viral population stopped changing while the ERV continues to accumulate muations.

If the viral material is capable of being passed host to host, than it can not have mutated to the extent of the ERVs that show large scale deletions.

What do you think about this question?

[BGoodForGoodSake]

What does the absence of exogenous material have to do with mutation rates? This is a rhetorical question.

Here is the crux of the issue. Retroviral material must pass from host to host and in the process the viral material changes. The question then is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse?

Endogenous material being the result of integration of viral material into a germ cell.

OK I realize it is rhetorical, but I feel it is an important question. In the abscense of an exogenous living population of an ERV all that is left changing is the ERV. When the ERV mutated enough it could no longer code for the virus and the viral population stopped mutating. The viral population stopped changing while the ERV continues to accumulate muations.

The term Endogenous here is applied only to the material which has found it's way into the host genome and then passed down through inheritance. Inserted material is not typically endogenous.
The viral population does not depend on endogenous material, it procreates via general retroviral insertions. The ERV is a special case.

Remember our discussion up to this point is based on the following postulate.
Let us assume that the viruses in question did indeed lead to the same insertion points across multiple species.

If the viral material is capable of being passed host to host, than it can not have mutated to the extent of the ERVs that show large scale deletions.

What do you think about this question?

The reason it was rhetorical is because it is not relevant to the discussion. The issue as it pertains to the discussion is, how much of the viral material changes as it is bouncing from host to host to finally be integrated into the genomes of the various species being discussed.

Because in your scenario a pandemic must have occured, the virus in discussion is infecting multiple species at the same time.
And the integration of these disparate(separate and unique) infections are the same. We are therefore only concerned with what must have happened. That the virus in question no longer exists doesn't matter, and in fact it isn't even sensical to compare the mutation rates (of ERV's since the dissapearance of the exogenous version of the virus to the mutation rates of the originating virus), because as you said there is nothing to compare.

So, lets stay on topic. The question is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse? This is the question I have been trying very patiently to pose to you. Please, if you could, answer this question.

And of course the related question was.
If I were to infect a chimpanzee and a human with the same retrovirus how much of the sequence of the insertions will be modified due the type(species) of cell it has infected?

[NewCreature]

What does the absence of exogenous material have to do with mutation rates? This is a rhetorical question.

Here is the crux of the issue. Retroviral material must pass from host to host and in the process the viral material changes. The question then is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse?

Endogenous material being the result of integration of viral material into a germ cell.

OK I realize it is rhetorical, but I feel it is an important question. In the abscense of an exogenous living population of an ERV all that is left changing is the ERV. When the ERV mutated enough it could no longer code for the virus and the viral population stopped mutating. The viral population stopped changing while the ERV continues to accumulate muations.

The term Endogenous here is applied only to the material which has found it's way into the host genome and then passed down through inheritance. Inserted material is not typically endogenous.
The viral population does not depend on endogenous material, it procreates via general retroviral insertions. The ERV is a special case.

Sure I agree that is true. With respect however to a proviral integrations and ERVs, which much of the endogenous material is assumed to be, they would functionally be the same. IT would appear that what you are asking is which would change faster a proviral integration or the retroviral particles that the infection is creating. The only benefit of the ERV sequence, above treating it is a standard proviral integration, is that heredity is another mechanism whereby mutations will accumulate in the ERV sequences (proviral integrations). Ignoring ERVs for a moment it would seem if we can show that proviral integrations mutate faster than the retroviral particles in the population it would leave no doubt that ERVs, with their added mechanisms whereby they change, change faster than a retroviral population.

What do you think about this question?

You did not respond to this point.

The reason it was rhetorical is because it is not relevant to the discussion. The issue as it pertains to the discussion is, how much of the viral material changes as it is bouncing from host to host to finally be integrated into the genomes of the various species being discussed.

Thankfully the viral particles are all transcribed from the same patterns, and they have little mechanism to accumulate all the various mutations in the population of infectious virions. Well I had to edit this a bit because I forgot to include an important point that I included in my response to a very similar question that you asked a couple of posts ago. And that is I still don't see how you can really seperate the provrial integrations be they ERVs or not from the retroviruses they code for. And for those proviral integrations no longer coding for a retrovirus we find of course that the proviral integration being the only thing changing changes more. While some think it is likely that avian flu will eventually mutate to the point that it can be passed among humans, it is very likley that the mutation that will lead to this change will be a result of the interaction of unique proteins involved in propagation of the proviral integration throughout a human host and the initial retroviral RNA genome. The mutation will likely happen in the proviral sequence in one of its integration sites that will begin to encode for infectious particles that will spread through a segment of the human population. The proviral sequence will be involved with a host of protiens and may be transcribed, integrated, and changed numerous times during its lifetime. These changes are how to effect the biggest changes in the population of retroviral virions. Changes in the pattern get communicated to the entire population. So while significant changes can happen it seems like we are talking about the possiblities of it happening, while ERVs have many more mechanisms by which the can be changed.

And the integration of these disparate(separate and unique) infections are the same. We are therefore only concerned with what must have happened. That the virus in question no longer exists doesn't matter, and in fact it isn't even sensical to compare the mutation rates (of ERV's since the dissapearance of the exogenous version of the virus to the mutation rates of the originating virus), because as you said there is nothing to compare.

No they won't be the same. They will be similar. I am not roped into one idea and during the course of investigation it is important to keep in mind that for most ERVs we don't see exogenous material in the environment capable of yielding the endogenous material. There is no reason to decree that all the reverse transcribed matter in the human genome is retroviral in origin.

You where the one that asked which changed more an ERV sequence or a population of retroviruses. I was simply pointing out that changes in the ERV caused the retroviral population to stop changing, and to stop even being coded for. This is likely to be what happens in many cases of immunity.

So, lets stay on topic. The question is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse? This is the question I have been trying very patiently to pose to you. Please, if you could, answer this question.

What is your answer to this question and why Much of the endogenous material that is passed from parent to child shows huge deletions. Heredity can account for the accumulation of mutations in the provrial integration, which is what we assume the ERV to be. Wouldn't the accumulation of mutations in the father's genome be copied into the gamete? While the female egg is a preexisting gamete from very early in a woman's life, the sperm from an older father contains the mutations in the ERVs sequence. The ERV would also be mutated by the combination of the gametes into a unique individual at conception as well.

If I were to infect a chimpanzee and a human with the same retrovirus how much of the sequence of the insertions will be modified due the type(species) of cell it has infected?

I don't know. The initial insertion would be the most similar between the two species because it would be carried out mostly by proteins within the virus itself. The propagation of the proviral sequence and course of infection will be less similar. The proteins involved will be different, and the two species may not both yield an infection, one could be immune.

Also what do you think about this?

[BGoodForGoodSake]

Sure I agree that is true. With respect however to a proviral integrations and ERVs, which much of the endogenous material is assumed to be, they would functionally be the same. IT would appear that what you are asking is which would change faster a proviral integration or the retroviral particles that the infection is creating.

No this is not what I am asking, how can I make this more clear?

*I'll use an example.

Several things to keep in mind when answering this question.

Remember the frame of time we are speaking of is within the period of integration in this scenario.
As a reminder the hypothesis is that the ERV's are a result of multiple insertion events in a single cross species pandemic.
All insertions mutations etc, are to be interpreted by the conditions to be expected if the hypothesis were true.

Lets say a virus infects host 1, then host 1 creates viral particles which infect host 2. Let's say it continues on down this way up to host 10,000. The virus somehow became integrated into host 1's germ cell and was passed down to his child. Are there likely to be more differences between the virus which infected host 1 and host 10,000, than there are between the integrated material between host 1's germ cell and the ERV of his progeny?

The two measurements are summarized below.

Difference in sequence between the original virus which infected host 1 and host 10,000.
Provirus in host 1's germ cell, the ERV sequence of all his/her descendents at the time the last host (host 10,000) is infected.
Which one is expected to show more discrepancies?

Please be aware of the timeframe, I cannot stress this enough.
P.S. I don't think I can clarify this question any further, whatever answer you give to this will be used in the analysis to follow.

The only benefit of the ERV sequence, above treating it is a standard proviral integration, is that heredity is another mechanism whereby mutations will accumulate in the ERV sequences (proviral integrations). Ignoring ERVs for a moment it would seem if we can show that proviral integrations mutate faster than the retroviral particles in the population it would leave no doubt that ERVs, with their added mechanisms whereby they change, change faster than a retroviral population.

We'll return to this once the questioning section is over.

What do you think about this question?

You did not respond to this point.

We'll return to this once the questioning has been completed. Suffice it to say the evidence shows that virl material changes at a much faster rate than endogenous material. But please do not respond to this until we have completed the groundwork.

Thankfully the viral ... by which the can be changed.

All very well and true, but not pertinent to this discussion as we shall see once we have completed this part of the discussion.

And the integration of these disparate(separate and unique) infections are the same. We are therefore only concerned with what must have happened. That the virus in question no longer exists doesn't matter, and in fact it isn't even sensical to compare the mutation rates (of ERV's since the dissapearance of the exogenous version of the virus to the mutation rates of the originating virus), because as you said there is nothing to compare.

No they won't be the same. They will be similar. I am not roped into one idea and during the course of investigation it is important to keep in mind that for most ERVs we don't see exogenous material in the environment capable of yielding the endogenous material. There is no reason to decree that all the reverse transcribed matter in the human genome is retroviral in origin.

You are right, they might not be. But we must examine each hypothesis critically and alone. This way we can remove each possibility. The hypothesis we are examining here is multiple insertion events within a single pandemic. Remember this problem began when you were using the solutions of multiple hypothesis to answer the various questions.

You where the one that asked which changed more an ERV sequence or a population of retroviruses. I was simply pointing out that changes in the ERV caused the retroviral population to stop changing, and to stop even being coded for. This is likely to be what happens in many cases of immunity.

But how can that be if a single population of virus infected multiple species? Obviously here within the context of your hypothesis the virus integrated into the genome of multiple species. The most likely scenario is a sequential integration. Don't you concur? If so then the virus must have infected the various populations for some time even after integrating into the genome of one species.

So, lets stay on topic. The question is, does the viral material passing from host to host change at a faster pace than endogenous material passed from parent to child or is it the reverse? This is the question I have been trying very patiently to pose to you. Please, if you could, answer this question.

What is your answer to this question and why Much of the endogenous material that is passed from parent to child shows huge deletions. Heredity can account for the accumulation of mutations in the provrial integration, which is what we assume the ERV to be. Wouldn't the accumulation of mutations in the father's genome be copied into the gamete? While the female egg is a preexisting gamete from very early in a woman's life, the sperm from an older father contains the mutations in the ERVs sequence. The ERV would also be mutated by the combination of the gametes into a unique individual at conception as well.

I am sorry but this does not address the comparison at all. I have reworded the question above marked with an *. Please send me a private message to discuss the question so we don't have to continue with this dance.
I would like to move on, as I am sure you do as well.

If I were to infect a chimpanzee and a human with the same retrovirus how much of the sequence of the insertions will be modified due the type(species) of cell it has infected?

I don't know. The initial insertion would be the most similar between the two species because it would be carried out mostly by proteins within the virus itself. The propagation of the proviral sequence and course of infection will be less similar. The proteins involved will be different, and the two species may not both yield an infection, one could be immune.

Also what do you think about this?

Ok good answer I will address this once all the questioning is complete.

**Bear in mind I did not counter every point, because I did not want to bog down my post. There are many points in this post I must address later. The focus of this post is to clarify the question which still need to be address by NewCreature.

As you have addressed one question I will pose the next question which needs to be addressed.
In your scenario, how long does it take for a single integration event to propogate, into the entire population(of a species)?Bear in mind that the scenario is multiple insertion events within a single cross-species pandemic.

I want to add that I appreciate the time you put into this discussion.