Aa
PMBC - Shown not to be viral reservoirs
http://natap.org/2008/HCV/030508_01.htm
The next logical step to deconstructing the evolution of the virus is that at one time it may have been an useful symbiote rather than a parasite (see mikesimon's recent posting about post transplant patients who beome totally virus free). A virus that only causes fatal complications in 20% of the population, and that generally not till later in life, wouldn't have any deselection pressures on it in a country like Afghanistan where the average lifespan is under 50. Even less so in Northern Europe 1000 years ago where the lifespan was even lower.
First, this is NOT my quote, so I do not know where the "DD" came from:
" RNA lifeforms mutate like crazy"-- DD < (not my DD, or comment)
Someone else must have posted the above comment.
Secondly, I think your above description and explanation is interesting, but assumes that the virus must be trying to 'hide', and therefore you proceed to negate that possibility. I do not think it is 'hiding', or anything like that. I believe, from what I am reading in the various studies, that the virus has been placed under immune system 'control' and is not likely to be doing anything at all of its own accord, but is just being kept at extremely low levels by the immune system. Maybe the immune system cannot fully exterminate the virus in these circumstances, and maybe in some people it eventually does. Hence the 10% or so that show up as having no persistent virus in PBMC, Lymph Nodes, Hepatocytes, etc. I think the virus may still be alive and well in the serum also, after the SVR, but at extremely low levels, under the limits of standard detection. It could be randomly at 1 copy / 20 IU of serum for instance, and would NEVER be detected on the most sensitive PCR tests. This would explain the six people who continued to go from undetected to very low level detected. Maybe the immune system varies in its ability to keep the virus at extremely low levels in the blood, and sometimes allows little detectable fluctuations to occur.
Finally, what you described is interesting to ponder, but is contradicted by the cold hard facts in every one of the linked research studies, but one, the initial linked study at the top of the thread. (and the study you linked did not use the most powerful amplified testing to look for the virus, either).
If the virus is showing up, and is detected by special amplified testing, and is replicating, then explaining why theoretically it cannot really happen becomes an exercise in futility, and an academic construct. If its there, then its there, and whether we theorize that it should not behave that way, or not, is a moot point. Its there. We need to figure out HOW it remains at low levels, and what the significance of this residual infection might be. Thats my take anyway. Let's also place DD notations on things that DD has said. Thanks.
DoubleDose
" RNA lifeforms mutate like crazy"-- DD < (not my DD, or comment)
Someone else must have posted the above comment.
Secondly, I think your above description and explanation is interesting, but assumes that the virus must be trying to 'hide', and therefore you proceed to negate that possibility. I do not think it is 'hiding', or anything like that. I believe, from what I am reading in the various studies, that the virus has been placed under immune system 'control' and is not likely to be doing anything at all of its own accord, but is just being kept at extremely low levels by the immune system. Maybe the immune system cannot fully exterminate the virus in these circumstances, and maybe in some people it eventually does. Hence the 10% or so that show up as having no persistent virus in PBMC, Lymph Nodes, Hepatocytes, etc. I think the virus may still be alive and well in the serum also, after the SVR, but at extremely low levels, under the limits of standard detection. It could be randomly at 1 copy / 20 IU of serum for instance, and would NEVER be detected on the most sensitive PCR tests. This would explain the six people who continued to go from undetected to very low level detected. Maybe the immune system varies in its ability to keep the virus at extremely low levels in the blood, and sometimes allows little detectable fluctuations to occur.
Finally, what you described is interesting to ponder, but is contradicted by the cold hard facts in every one of the linked research studies, but one, the initial linked study at the top of the thread. (and the study you linked did not use the most powerful amplified testing to look for the virus, either).
If the virus is showing up, and is detected by special amplified testing, and is replicating, then explaining why theoretically it cannot really happen becomes an exercise in futility, and an academic construct. If its there, then its there, and whether we theorize that it should not behave that way, or not, is a moot point. Its there. We need to figure out HOW it remains at low levels, and what the significance of this residual infection might be. Thats my take anyway. Let's also place DD notations on things that DD has said. Thanks.
DoubleDose
And again....all I pull up when I copy/paste that sight (as others I try here) it brings up this post, not the article. What am I doing wrong? Want to read that!
LL
LL
The following does not speak to any position I have about post-SVR viral persistence, the role, if any, of PBMC,or the inhabitation of any other cell suspected of a role in the HCV lifecycle. I will get to that pretty soon I hope, as many have raised some very interesting points, and I do have some studies to share that may (or may not) illuminate some areas of this topic. I would rather wait for now until I can be assured of some continuity on my part--otherwise I'll get lost. Lately my ability to remain focused has been off somewhat.
The following is some science along with a sprinkling of conjecture, and a dash of what hopefully will appear to be logic. I usually don’t stray too far from the scientific path when it comes to HCV, but speculation can be thought provoking at times and fun to share.
" RNA lifeforms mutate like crazy"-- DD
This is a very good reason why it wouldn’t be necessary for HCV to convalesce or 'hibernate', go dormant,etc, as a means to ensure it’s continued existence. HCV is the fastest mutating virus ever discovered to this point in history. Its apparent survival strategy is quite simple--mutate so fast that the immune system is overwhelmed. A plan of diversion on a grand scale---from thousands to millions of mutations (quasi-species) per lifecycle by each infective virion. And every one of them is unique.( It is through this process that new genotypes/subtypes will rise. )
HCV seeks its lowest state of free energy. Don't we all ? ;) Another way of stating this is to say that through phylogenesis it has become as efficient as possible . To illustrate this phenomenon consider the following: HCV in its past history has shed replication mechanisms that were at one time needed for its survival. As we all know HCV cannot replicate by itself. It relies on its innate ability to manipulate the host cell’s replication processes to produce viral copies for it. This leads many evolutionary biologists to surmise that at one time in the history of HCV it must have had the ability to replicate using its own viral properties.Once the virus eventually unlocked the ‘code’ of a host cells replicating mechanisms it no longer needed to expend any energy on replication---a process which it previously had needed for survival. The ‘parts’ of the viral assembly that allowed the virus to self-replicate were eventually eliminated (devolution) or shed, in the never ending goal towards maximum efficiency (lowest energy state). For HCV to develop and/or keep another mechanism for survival when it already possesses one that requires almost zero energy (extremely efficient) while at the same time being unbelievably prodigious (an almost perfect machine), would be an expenditure of energy that would appear to be antithetical to the goal of reaching its lowest state of energy (becoming most efficient). It would serve the virus absolutely no purpose to develop (or keep) another process for survival, such as entering cells to 'hide', especially since doing so has never been shown to result in a release,delayed or otherwise of infective HCV back into the sera where it could be available for an opportunity to infect a new host. If HCV is to succeed in its drive to remain in existence it is absolutely imperative that infective forms of the virus are readily available whenever a transmission vector presents itself. Being blood borne necessarily limits HCV in the opportunities it will have to ensure its perpetuity. Passing infection via blood to blood contact is one of the most inefficient means of transference known. (Let’s pray it stays this way so that HCV, as well as a host of other viruses, never mutate to ‘aerosol’ form). Since these events of exposure are rare and cannot be predicted, the virus can ill afford the luxury of ‘hiding’, going dormant, or convalescing for very long if it wants to continue to be.
The following is some science along with a sprinkling of conjecture, and a dash of what hopefully will appear to be logic. I usually don’t stray too far from the scientific path when it comes to HCV, but speculation can be thought provoking at times and fun to share.
" RNA lifeforms mutate like crazy"-- DD
This is a very good reason why it wouldn’t be necessary for HCV to convalesce or 'hibernate', go dormant,etc, as a means to ensure it’s continued existence. HCV is the fastest mutating virus ever discovered to this point in history. Its apparent survival strategy is quite simple--mutate so fast that the immune system is overwhelmed. A plan of diversion on a grand scale---from thousands to millions of mutations (quasi-species) per lifecycle by each infective virion. And every one of them is unique.( It is through this process that new genotypes/subtypes will rise. )
HCV seeks its lowest state of free energy. Don't we all ? ;) Another way of stating this is to say that through phylogenesis it has become as efficient as possible . To illustrate this phenomenon consider the following: HCV in its past history has shed replication mechanisms that were at one time needed for its survival. As we all know HCV cannot replicate by itself. It relies on its innate ability to manipulate the host cell’s replication processes to produce viral copies for it. This leads many evolutionary biologists to surmise that at one time in the history of HCV it must have had the ability to replicate using its own viral properties.Once the virus eventually unlocked the ‘code’ of a host cells replicating mechanisms it no longer needed to expend any energy on replication---a process which it previously had needed for survival. The ‘parts’ of the viral assembly that allowed the virus to self-replicate were eventually eliminated (devolution) or shed, in the never ending goal towards maximum efficiency (lowest energy state). For HCV to develop and/or keep another mechanism for survival when it already possesses one that requires almost zero energy (extremely efficient) while at the same time being unbelievably prodigious (an almost perfect machine), would be an expenditure of energy that would appear to be antithetical to the goal of reaching its lowest state of energy (becoming most efficient). It would serve the virus absolutely no purpose to develop (or keep) another process for survival, such as entering cells to 'hide', especially since doing so has never been shown to result in a release,delayed or otherwise of infective HCV back into the sera where it could be available for an opportunity to infect a new host. If HCV is to succeed in its drive to remain in existence it is absolutely imperative that infective forms of the virus are readily available whenever a transmission vector presents itself. Being blood borne necessarily limits HCV in the opportunities it will have to ensure its perpetuity. Passing infection via blood to blood contact is one of the most inefficient means of transference known. (Let’s pray it stays this way so that HCV, as well as a host of other viruses, never mutate to ‘aerosol’ form). Since these events of exposure are rare and cannot be predicted, the virus can ill afford the luxury of ‘hiding’, going dormant, or convalescing for very long if it wants to continue to be.
Thanks for the Health Pages compendium of articles and studies regarding 'occulr HCV, persistent HCV after SVR, and related topics. I did not even realize just how many papers had been published documenting and explaining this phenomenon. For anyone who really wants to understand where we are today with this issue, and what exactly seems to be happening in our bodies after SVR, this listing of studies is the most comprehensive that I have come across. Thanks for taking the time and trouble to compile all this information, and to make it readily available to all of us. Great reading for a rainy day!
Reading these studies also makes you realize how much more there is to learn about the virus, and why we can't stop with the current treatment regimes thinking we have solved the riddles, and provided the total cure. We need lots of follow up to determine what this form of residual infection does to us, what its level of infectivity and transmission might or might not look like, and to also understand more about what the general population really looks like vis-a-vis HCV infection, in all its forms.
Questions like, does occult HCV occur only in those who have treated...is occult exactly the same entity as 'persistent HCV after SVR, are their many people out there with undetected, antibody-negative HCV occult infections??? Where does this infection originate from in cases where it seems ideopathic? Does this 'little, compartmentalized infection cause any of the familiar extra-hepatic symptoms/// Does our immune system begin to create auto-immune illnesses or disorders as a result of occult or persistent HCV??? The list of things we need to understand goes on and on.
I think we are really just at the threshold of understanding regarding the life and behavior of HCV. The researchers will have a field day exploring all the peripheral issues.
Thanks again for the great resource.
DoubleDose
Reading these studies also makes you realize how much more there is to learn about the virus, and why we can't stop with the current treatment regimes thinking we have solved the riddles, and provided the total cure. We need lots of follow up to determine what this form of residual infection does to us, what its level of infectivity and transmission might or might not look like, and to also understand more about what the general population really looks like vis-a-vis HCV infection, in all its forms.
Questions like, does occult HCV occur only in those who have treated...is occult exactly the same entity as 'persistent HCV after SVR, are their many people out there with undetected, antibody-negative HCV occult infections??? Where does this infection originate from in cases where it seems ideopathic? Does this 'little, compartmentalized infection cause any of the familiar extra-hepatic symptoms/// Does our immune system begin to create auto-immune illnesses or disorders as a result of occult or persistent HCV??? The list of things we need to understand goes on and on.
I think we are really just at the threshold of understanding regarding the life and behavior of HCV. The researchers will have a field day exploring all the peripheral issues.
Thanks again for the great resource.
DoubleDose
I just spent about an hour trying to rearrange the papers in chronological order on the 'Occult' Health Page. It appears as if the software has some serious bugs over there. After putting things in order I saved it - and the mess that is now there is what the program put up. And, I don't seem to be able to edit any of what is there ...... double whammy. I tried to delete the mess and replace it by C&P'ing a previous 'good' revision. No go. I just keeps putting the same mess back up again.
No time to try and fix it now. I'll see if there's anything more that can be done tomorrow.
TnHepGuy
No time to try and fix it now. I'll see if there's anything more that can be done tomorrow.
TnHepGuy
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
