Aa
What causes the damage
Trying to understand this alien life form thats invaded my body. I thought I remembered from school many years ago that all life must eat or consume some sort of nourishment. Apparently thats not true on the virus level of life. Next is propagation, which is the goal of all life and apparently that of our little wiggly friends. Usually parisites do not harm the host organism. So I take it the damage to our livers is the result of it working overtime to rid us of this bug. Is this correct.
HCV isn't just a "bag of chemicals, in my opinion, but neither do I believe it is life, in the scientific sense. The chemicals found in HCV are necessary to create bonds through electrophoresis which causes attractions and repulsions. Combined with electrostatic forces this is what "holds" the virus together in its shape and allows the virus to perform self-assembly, as well as the many functions needed for the virus to exist, such as signaling . Chemicals are the "glue" that holds it together. HCV is every bit as efficient in what it does as today's computers, and MUCH faster. Scientists have been exploring ways of incorporating molecular biology with computer science for many years and they are making progress.. By incorporating biologically derived "switches" it is theorized that computers will be able to reach much faster computing times.
Quasi-species: I've said it many times. No serious discussion about HCV eradication can be held without addressing the nature of HCV mutational abilities. Most of you may know the following but for the sake of those who want to learn I'll give what I hope is a coherent description. One way to describe QS is this: Imagine a line, and on this line are round clusters of tightly packed little dots.
These single points are so tightly packed together they resemble a large solid black ball surrounded by what appears to be a halo of slightly less packed dots. These large clusters are spaced apart unevenly almost down the entire length of this line. These are the places on the line (genome) where the genotypes reside. The large dense clusters represent closely packed HCV variants that are almost identical and which indicate the residence of a major genotype. This means that a genotype of one variety have variants that are not all assembled in identically the same way. However these slightly varied viruses are so similar that they practically have their “homes” in almost the same place on the line. The smaller clusters in the 'halo' surrounding the large cluster are the subtypes (a,b,c,d, etc) and all are almost the identical distance to the residence of the genotype. As you move away from these on the line they begin to thin out more and more until the clusters are much smaller than the subtypes. They are far away from the home of the genotype closest to them and are loosely scattered on the line. This is where the quasi-species reside.
Quasi-species (mutations) give rise to new subtypes and genotypes but the occurrences are rare. Success is what determines a new genotype, or subtype. If a quasi-species is produced which shows success, the virus will produce more of this variant (mutation). If the success continues, more and more of this variant and others extremely closely related will end up residing very near to the same place on the genome in great numbers. This may result some day in the creation of a new genotype. But QS serve the virus in more ways than giving rise to new infectious and durable variants. They are also used to confuse the immune system. Most QS exist for just seconds or minutes as they are very unstable. But that's plenty of time to trigger a immune response(s) designed for that particular virus particle that was encountered, and to even order up more of the same defenses from surrounding cells. Now, imagine thousands of these QS being produced each day distracting our immune mechanisms from focusing on the primary geno/subtype that is causing our chronic infection.
Staying with the imaginary line representing the genome consider this: When the geno/subtype comes under immune pressure the production of QS diversity increases through chemical signaling in an attempt to confuse our immune mechanisms. This does not mean an increase in viral load necessarily, which would be measurable. It means an increase in diversity among the quasi-species. When the immune pressure lets up the geno/subtype will return to its 'ancestral home' on the genome.
Devolution: Evolutionary biologists see phenomena all the time that can only be explained by devolution. HCV is a classic example. It is against all probability that HCV had the capacity from the beginning to hijack a cell's replication mechanisms for its own propagation. So, it is surmised that it must have had the capacity at one time to multiply on its own. It is believed this type of ability to use another cells chemical machinery is the product of evolution, where many failures eventually over time finally resulted in success. Once HCV 'learned ' how to replicate without using its own devices it no longer needed the 'parts' necessary to perform this task on its own. So, it simply discarded them, thereby reducing the energy it needed to exist. Over time it has rid itself of all unnecessary functions while still maintaining the properties necessary to remain viable, seeking even lower states of free energy. It now has so little energy it cannot be detected through any means today. When destroyed it does not even give off an energy signature.
Is HCV alive ? It has been possible for some time to create the same chemical compounds necessary for life to exist here. These chemicals (enzymes) are indeed referred to as the building blocks of life. But in my view these compounds are as far away from being life as a single log is from being a cabin.
Quasi-species: I've said it many times. No serious discussion about HCV eradication can be held without addressing the nature of HCV mutational abilities. Most of you may know the following but for the sake of those who want to learn I'll give what I hope is a coherent description. One way to describe QS is this: Imagine a line, and on this line are round clusters of tightly packed little dots.
These single points are so tightly packed together they resemble a large solid black ball surrounded by what appears to be a halo of slightly less packed dots. These large clusters are spaced apart unevenly almost down the entire length of this line. These are the places on the line (genome) where the genotypes reside. The large dense clusters represent closely packed HCV variants that are almost identical and which indicate the residence of a major genotype. This means that a genotype of one variety have variants that are not all assembled in identically the same way. However these slightly varied viruses are so similar that they practically have their “homes” in almost the same place on the line. The smaller clusters in the 'halo' surrounding the large cluster are the subtypes (a,b,c,d, etc) and all are almost the identical distance to the residence of the genotype. As you move away from these on the line they begin to thin out more and more until the clusters are much smaller than the subtypes. They are far away from the home of the genotype closest to them and are loosely scattered on the line. This is where the quasi-species reside.
Quasi-species (mutations) give rise to new subtypes and genotypes but the occurrences are rare. Success is what determines a new genotype, or subtype. If a quasi-species is produced which shows success, the virus will produce more of this variant (mutation). If the success continues, more and more of this variant and others extremely closely related will end up residing very near to the same place on the genome in great numbers. This may result some day in the creation of a new genotype. But QS serve the virus in more ways than giving rise to new infectious and durable variants. They are also used to confuse the immune system. Most QS exist for just seconds or minutes as they are very unstable. But that's plenty of time to trigger a immune response(s) designed for that particular virus particle that was encountered, and to even order up more of the same defenses from surrounding cells. Now, imagine thousands of these QS being produced each day distracting our immune mechanisms from focusing on the primary geno/subtype that is causing our chronic infection.
Staying with the imaginary line representing the genome consider this: When the geno/subtype comes under immune pressure the production of QS diversity increases through chemical signaling in an attempt to confuse our immune mechanisms. This does not mean an increase in viral load necessarily, which would be measurable. It means an increase in diversity among the quasi-species. When the immune pressure lets up the geno/subtype will return to its 'ancestral home' on the genome.
Devolution: Evolutionary biologists see phenomena all the time that can only be explained by devolution. HCV is a classic example. It is against all probability that HCV had the capacity from the beginning to hijack a cell's replication mechanisms for its own propagation. So, it is surmised that it must have had the capacity at one time to multiply on its own. It is believed this type of ability to use another cells chemical machinery is the product of evolution, where many failures eventually over time finally resulted in success. Once HCV 'learned ' how to replicate without using its own devices it no longer needed the 'parts' necessary to perform this task on its own. So, it simply discarded them, thereby reducing the energy it needed to exist. Over time it has rid itself of all unnecessary functions while still maintaining the properties necessary to remain viable, seeking even lower states of free energy. It now has so little energy it cannot be detected through any means today. When destroyed it does not even give off an energy signature.
Is HCV alive ? It has been possible for some time to create the same chemical compounds necessary for life to exist here. These chemicals (enzymes) are indeed referred to as the building blocks of life. But in my view these compounds are as far away from being life as a single log is from being a cabin.
I believe that current thought is that the virus may, to some degree, be cytopathic but the major damage to our liver is done by our immune system's response to the virus.
If the virus was itself highly cytopathic we should see liver damage correspond closely to viral load - the more virus the more damage, if the virus, in and of itself, was highly cytopathic. We know that is not the case however. We have seen significant damage in patients with a relatively low viral load and minimal damage in patients with a relatively high viral load. So it is our immune system's response to the virus that causes the real damage. And when our immune system mounts an attack, like in war, there is often collateral damage and innocent uninfected bystander cells come under attack as well as the infected cells. That probably explains why a patient can have very significantly elevated enzymes - which reflect significant cell death - and yet have a low viral load. The uninfected cell are "dying" too.
Mike
If the virus was itself highly cytopathic we should see liver damage correspond closely to viral load - the more virus the more damage, if the virus, in and of itself, was highly cytopathic. We know that is not the case however. We have seen significant damage in patients with a relatively low viral load and minimal damage in patients with a relatively high viral load. So it is our immune system's response to the virus that causes the real damage. And when our immune system mounts an attack, like in war, there is often collateral damage and innocent uninfected bystander cells come under attack as well as the infected cells. That probably explains why a patient can have very significantly elevated enzymes - which reflect significant cell death - and yet have a low viral load. The uninfected cell are "dying" too.
Mike
"Ewwww.... disgusting little aliens in my body". Sometimes the motivation for some people to treat hcv. It's not always just a matter of the right time to treat due to the meds available now or down the road or the current physical situation a person might be in. Sometimes it's the situation in their head in which is the determining factor in the the 'treat or not to treat' decision process. One of the reasons that I think that the approach to hcv is unique to each person. Not all stage 2/grade 2 people are equal, for example.
This is freaky... I haven't read through the articles, yet, but will when I get the time.
Sometimes when I am really, really tired and lie down to rest, I have the sensation of all these little buggers cribbling around in my blood all through my body. It's like I can feel the viruses... millions of them all over. One doesn't really know what they are up to, but surely a lot of mischief. Ewwww.... disgusting little aliens in my body....
BTW, I'm not on anything and I haven't been for many years. maybe just vivid imagination, but it's kind of freaky.
Marcia
Sometimes when I am really, really tired and lie down to rest, I have the sensation of all these little buggers cribbling around in my blood all through my body. It's like I can feel the viruses... millions of them all over. One doesn't really know what they are up to, but surely a lot of mischief. Ewwww.... disgusting little aliens in my body....
BTW, I'm not on anything and I haven't been for many years. maybe just vivid imagination, but it's kind of freaky.
Marcia
"It's alive!" (It echoes in my head like a cheesy Halloween commercial lol.)
At least, that's what I've always thought, anyway. In some ways, the virus IS the ultimate organism -- able to persist in its function and progenation in spite of destruction or mutation. Besides, I'd feel almost a little cheated if it was just a bunch of "inert chemicals" putting everyone through all these changes! :P
Thanks for the great article.
~eureka
At least, that's what I've always thought, anyway. In some ways, the virus IS the ultimate organism -- able to persist in its function and progenation in spite of destruction or mutation. Besides, I'd feel almost a little cheated if it was just a bunch of "inert chemicals" putting everyone through all these changes! :P
Thanks for the great article.
~eureka
Just about to post link http://www.****.com .Decided to refresh page first and saw you beat me to it. Also has good seminar on antifibrotic therapy. Thanks guys very informative thread.
--George--
--George--
Thanks, Links; re stellate cells:
http://www.medscape.com/viewarticle/436461_3
(Again, free registration required)
Bill
http://www.medscape.com/viewarticle/436461_3
(Again, free registration required)
Bill
my crude "lay" understanding is that the body produces stellate cells to fight the virus, and these cells cause the scarring. in other words, if the body did not respond the way it does, the virus itself would cause no harm.
Eye-opener indeed, George. I don’t pretend to understand much of this, but that paper kind of dumps the world on its arse, huh? It left me wondering if the plant and animal kingdoms aren’t just fodder for the real masters of this planet. I rarely smoke pot anymore, but maybe I’ll try reading this stoned some day and see if I get any more out of it :o).
Glad you enjoyed, and good luck—
Bill
Glad you enjoyed, and good luck—
Bill
If what you are saying is correct than the hep virus must be changing the hepatocytes cells for our immune system to see them as alien and a threat. I read the average life span of the hepatocyte is 5 months and they are able to regenerate. Does the hep hamper regeneration or is the kill rate faster than the regeneration rate.
The theory that is backed by the most evidence and which receives the most support amongst researchers, is that the destruction of hepatocytes is done by our own immune defense mechanisms. In other words, we are doing it to ourselves.
Mr Liver
Mr Liver
Wow, Bill I am completely dumbfounded. I read that article in a state awe. Certainly questions the definition of life. If you do define virus as life in a way it could be the ultimate life form and maybe the predecessor of all life or at least a major player in evolution. The section on phoenix phenotype where it can basically come back from the dead or bring cells back to life is amazing. Can relapses have anything to do with this. Going back for my third reading. Thanks for a real eye opener. ---George--
“Apparently thats not true on the virus level of life”.
Viruses are thought by some to bridge the gap between chemistry and life; you might find this article very interesting:
http://www.uvm.edu/~biology/Classes/011/alive.pdf
This article discusses some of the basic building blocks of virus, and also questions whether they are actually living organisms or “bags of chemicals”.
Bill
Viruses are thought by some to bridge the gap between chemistry and life; you might find this article very interesting:
http://www.uvm.edu/~biology/Classes/011/alive.pdf
This article discusses some of the basic building blocks of virus, and also questions whether they are actually living organisms or “bags of chemicals”.
Bill
The answer is actually that the Hepatitis C virus uses human liver cells as factories to replicate.
The viron alights on a liver cell which embraces it.The viron creates a small nunber of replicas within the cell.The original viron reaches the end of it's life whilst the invaded liver cell dies releasing the replicas into the blood stream to start the process anew.
The viron alights on a liver cell which embraces it.The viron creates a small nunber of replicas within the cell.The original viron reaches the end of it's life whilst the invaded liver cell dies releasing the replicas into the blood stream to start the process anew.
The virus lives in our blood. The liver is our purifyer. After years of being under attack some of us, though far from all, have liver damage.
Ironically, the alien can eventually kills its host. Sounds kind of like us on planet earth, doesn't it?
Ironically, the alien can eventually kills its host. Sounds kind of like us on planet earth, doesn't it?
Dunno enough to say if you are "correct" or "incorrect". My understanding is that the virus causes both inflammation and changes within liver cells-- now whether this is a result of the liver "fighting," or if it's a result of direct viral damage, or some other pathway I couldn't say, but maybe someone more knowledgeable on the microbiology will help out.
I definitely think you made an interesting point, though, about how "usually parasites do not harm the host..." I have a crazy theory, but here goes:
Maybe historically it's always been there, sustained by us, but we (as a human race) just haven't lived long enough until now to see "long-term" damage. Perhaps when HCV evolved into the human host (tens, hundreds, thousands? of years ago, who knows) it never expected the host to live long enough to recognize it as an enemy.
It's an amusing thought to ponder that we've outlived HCV's life expectancy for us.
~eureka
I definitely think you made an interesting point, though, about how "usually parasites do not harm the host..." I have a crazy theory, but here goes:
Maybe historically it's always been there, sustained by us, but we (as a human race) just haven't lived long enough until now to see "long-term" damage. Perhaps when HCV evolved into the human host (tens, hundreds, thousands? of years ago, who knows) it never expected the host to live long enough to recognize it as an enemy.
It's an amusing thought to ponder that we've outlived HCV's life expectancy for us.
~eureka
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