Aa
Cell to Cell transfer of hec-c
I am really surprised that know one responed to my earlier post. This research paper explains more about why some people handle the virus and others don't and most important why viral load means nothen. With cell to cell transfer there is no way that TX is going to work. I suggest you all read this. It explains why the virus moves so slow in most and can replicate so fast in others. As I always thought and the numbers bear me out, you are more likely to die with the virus than because of it. Sure its causing damage slowly but for the most part if you don't have cell to cell transference your bodies own imune system will keep it at bay. There is a lot we still don't know about this virus and it bothers me some to see the fear factor so high that some jump into treatment with the chance of doing more harm than good.
Ron
Ron
oh my, LOL, your note reminded me of myself as i started to explore the incredible world of hcv.
one question leads to many others, time consuming to delete flaws in conclusions, time consuming to fill in the gaps of understanding. i am no expert by a long shot as i still have some big gaps, but time and persistance has been a friend along with many peers and their excellent discussions/debates and wisdom from experts like HR. another valuable base to focus study on is cell and viral biology along with the human immune function. lol a math degree may be challenged but certainly be an asset in comprehension on the molecular side of things! then there is the school of hard knocks...sure to teach you some important lessons.
well to take on the "Q"s as i can read em
CTC replication has No effect on ribavirin circulating and plasma levels, nor in riba's intracellular function.
the exact mechanism of ribavirin in the function of viral kinetics is still not well understood but some studies show it accelerates phase 2 fall in hcv rna.( very important to get that viral load down early in treatment for prediction of tx response). the lethal mutagenesis effect of riba causing hcv error catastrophe only partially explains its effect on viral kinetics. as evidenced by ribavirin mono trials inability to reduce viral rna. there is a theory well described by a researcher called Sallie that explains the anti viral effects of ribavirin to be more due to replicative homeostasis as opposed to error castrophe. the article is tough reading though. (will give a link below). riba also effects immune modulation and stimulation in concert with IFN synergistically, and that is why it not only functions importantly in the beginning to reduce viral loads but also to reduce relapse thus SVR rates. however as we know all genotypes are not created equal in terms of response to SOC. the reasons being not only host related but perhaps better explained by viral charactersitics.
high dose riba has its inherent risks not only with life threatening anemia but in renal impairment.
i am like many others impressed with some reports that state high dose riba (1600-4000 mg/day) changes SVR rate in geno 1 from 50% to 90%. however there are not enough studies to confirm or recommend this due to this dose is above recommendation and the associated SAE's.
our resident expert JIM can certainly give alot more info about this than i can. so high dose riba may in this regard profoundly effect those early viral kinetics to favor rapid viral rna decline to achieve that undetected sooner (but only in combination with IFN) but as i said there are risks and one should only do this with the support of an experienced hepatologist.
when i did my treatment (geno3) i had a negative predictive factor of age and high viral load. i pushed for higher dose riba max wt based even though it has not been proven to increase SVR in my geno. however my doc agreed and by week 4 i was undetected. i personally believe the extra riba may have been a factor as my pre-tx viral load was over 20 mill. for sure it did not hurt! although again with my geno a 4wk undetect is more likely the norm but relapse rate still not understood well. another reason i stayed on the wt based dose through out tx. btw i did SVR and for me my tx regimen was a success. would be interesting to compare me to me taking the 800mg recommended riba dose for my geno. i will never know this difference and glad of it.
so therapeutic or high dose riba has no relationship to CTC infectivity. you are right to conclude this.
longer duration in SOC has been shown to increase SVR in some response patterns such as relapse and partial responders. i think this is due more to viral charactersitics/mutations that respond favorably to longer dose regimens.
in regards to fat or other organs where hcv hides. in my understanding hcv does not hide out in other organs, but has been proven to be able to replicate in other cells in the body outside the liver (its [liver] best and preferred medium for replicative success)perhaps thus providing a reservoir to some degree. how this fact influences its ability to cause disease outside of the liver is still not well understood and debated. HR has explained the durabilty of SVR and this would support any reservoirs of virus out side the liver would not be disease causing once SVR is achieved.
it is known that hcv increases risk of lympoproliferative diseases and alters immune function(along with IFN) that may be the genesis for other immune related diseases. also Hr explained well the relationship of immune stress caused by inflammation especially with his leaky bowel pathogenesis of circulating immune complexes systemically as well as localy in the hepatocyte. the evidence of its tropism has not proven to directly result in other diseases....but the jury may still be out in this regard as i understand it. without getting in occult virus which is another subject all together.
i hope this helps.. for sure HR and others can give alot more meat into your questions.
hope you are feeling well. sometimes study is a great way to divert anxiety. it sure helped mine although i am not as diligent as i was on treatment perhaps my understanding is improving without the effects of tx meds and SVR. some articles you may enjoy
http:www.medscape.com/viewarticle/543530 explains viral kinetics of riba and IFN
also http://www.virologyj.com/content/4/1/29 replicative homeostasis by Sallie good luck....it may take several readings to get his gist. however it is for sure a most excellent explanation and worth the study time to understand it.
hugs Whrose
one question leads to many others, time consuming to delete flaws in conclusions, time consuming to fill in the gaps of understanding. i am no expert by a long shot as i still have some big gaps, but time and persistance has been a friend along with many peers and their excellent discussions/debates and wisdom from experts like HR. another valuable base to focus study on is cell and viral biology along with the human immune function. lol a math degree may be challenged but certainly be an asset in comprehension on the molecular side of things! then there is the school of hard knocks...sure to teach you some important lessons.
well to take on the "Q"s as i can read em
CTC replication has No effect on ribavirin circulating and plasma levels, nor in riba's intracellular function.
the exact mechanism of ribavirin in the function of viral kinetics is still not well understood but some studies show it accelerates phase 2 fall in hcv rna.( very important to get that viral load down early in treatment for prediction of tx response). the lethal mutagenesis effect of riba causing hcv error catastrophe only partially explains its effect on viral kinetics. as evidenced by ribavirin mono trials inability to reduce viral rna. there is a theory well described by a researcher called Sallie that explains the anti viral effects of ribavirin to be more due to replicative homeostasis as opposed to error castrophe. the article is tough reading though. (will give a link below). riba also effects immune modulation and stimulation in concert with IFN synergistically, and that is why it not only functions importantly in the beginning to reduce viral loads but also to reduce relapse thus SVR rates. however as we know all genotypes are not created equal in terms of response to SOC. the reasons being not only host related but perhaps better explained by viral charactersitics.
high dose riba has its inherent risks not only with life threatening anemia but in renal impairment.
i am like many others impressed with some reports that state high dose riba (1600-4000 mg/day) changes SVR rate in geno 1 from 50% to 90%. however there are not enough studies to confirm or recommend this due to this dose is above recommendation and the associated SAE's.
our resident expert JIM can certainly give alot more info about this than i can. so high dose riba may in this regard profoundly effect those early viral kinetics to favor rapid viral rna decline to achieve that undetected sooner (but only in combination with IFN) but as i said there are risks and one should only do this with the support of an experienced hepatologist.
when i did my treatment (geno3) i had a negative predictive factor of age and high viral load. i pushed for higher dose riba max wt based even though it has not been proven to increase SVR in my geno. however my doc agreed and by week 4 i was undetected. i personally believe the extra riba may have been a factor as my pre-tx viral load was over 20 mill. for sure it did not hurt! although again with my geno a 4wk undetect is more likely the norm but relapse rate still not understood well. another reason i stayed on the wt based dose through out tx. btw i did SVR and for me my tx regimen was a success. would be interesting to compare me to me taking the 800mg recommended riba dose for my geno. i will never know this difference and glad of it.
so therapeutic or high dose riba has no relationship to CTC infectivity. you are right to conclude this.
longer duration in SOC has been shown to increase SVR in some response patterns such as relapse and partial responders. i think this is due more to viral charactersitics/mutations that respond favorably to longer dose regimens.
in regards to fat or other organs where hcv hides. in my understanding hcv does not hide out in other organs, but has been proven to be able to replicate in other cells in the body outside the liver (its [liver] best and preferred medium for replicative success)perhaps thus providing a reservoir to some degree. how this fact influences its ability to cause disease outside of the liver is still not well understood and debated. HR has explained the durabilty of SVR and this would support any reservoirs of virus out side the liver would not be disease causing once SVR is achieved.
it is known that hcv increases risk of lympoproliferative diseases and alters immune function(along with IFN) that may be the genesis for other immune related diseases. also Hr explained well the relationship of immune stress caused by inflammation especially with his leaky bowel pathogenesis of circulating immune complexes systemically as well as localy in the hepatocyte. the evidence of its tropism has not proven to directly result in other diseases....but the jury may still be out in this regard as i understand it. without getting in occult virus which is another subject all together.
i hope this helps.. for sure HR and others can give alot more meat into your questions.
hope you are feeling well. sometimes study is a great way to divert anxiety. it sure helped mine although i am not as diligent as i was on treatment perhaps my understanding is improving without the effects of tx meds and SVR. some articles you may enjoy
http:www.medscape.com/viewarticle/543530 explains viral kinetics of riba and IFN
also http://www.virologyj.com/content/4/1/29 replicative homeostasis by Sallie good luck....it may take several readings to get his gist. however it is for sure a most excellent explanation and worth the study time to understand it.
hugs Whrose
whroose
thanks for that great response, and I need all the help I can get, so between the two or you, (HR) I'm getting the idea albeit slowly on some of this.
Just so you know, you're not a light weight, I'd not go there my friend, cause you are great
PS. I have all the autoimmune stuff you do, oiy, and a hornets nest in my liver this year, so it's hard to get caught up to speed in the middle of this horserace, so to speak,
but indulge me one more dumb question if you will:
and HR as well, or at least to ponder:
somewhere in here I think, Lord who knows where cause if life depended I probably couldn't recall enough of the wording to pull it up again with this search engines limitations,
, I seem to remember that the Riba worked by, in laymens terms, chopping up the RNA/DNA and thus interrupting the normally voracious replication aspects of the virus.
If this is not faulty memory on my part, then I would have to assume this means it get's done having penetrated the outer coat of the virus, sticky lipids or not, it has to get INTO the cell to effect the RNA strands before it can start chopping, and are these not inside the viral structure for the most part??
If this is true then, that Riba has to get inside,
and then on the assumtion all cells are serviced to some degree by the bloodstream,
it means the Riba is getting around,
in which case whether the virus can do cell to cell transfer or not,
what real difference would that make assuming the saturation point of the Riba stays high enough? And, would not this somewhat explain then why the higher dosing seems to yield the more reliable results?
I mean since blood carries the Riba to every cell I'm just not sure the cell to cell replication is really a matter for alarm.
I did wonder a while back, could fat retain virus since it get's less blood supply proportionately,
also wondering could bone matter itself be a hiding place.
but ultimately my main question is, even given a circutous route through the circulation before a Riba molecule reaches a neighboring infected cell let's say,
won't each cell still ultimately get serviced with Riba soon enough....
and if often and long enough in duration then why would it matter so much???
And, isn't that what the SOC is basically now proving out to a greater degree?
Isn't the longer duration tx resulting in people going UND for years now??
ok so that's not just one question....so much for my one time math major!!!!!!
: )))))))))))))))))))))
thanks for that great response, and I need all the help I can get, so between the two or you, (HR) I'm getting the idea albeit slowly on some of this.
Just so you know, you're not a light weight, I'd not go there my friend, cause you are great
PS. I have all the autoimmune stuff you do, oiy, and a hornets nest in my liver this year, so it's hard to get caught up to speed in the middle of this horserace, so to speak,
but indulge me one more dumb question if you will:
and HR as well, or at least to ponder:
somewhere in here I think, Lord who knows where cause if life depended I probably couldn't recall enough of the wording to pull it up again with this search engines limitations,
, I seem to remember that the Riba worked by, in laymens terms, chopping up the RNA/DNA and thus interrupting the normally voracious replication aspects of the virus.
If this is not faulty memory on my part, then I would have to assume this means it get's done having penetrated the outer coat of the virus, sticky lipids or not, it has to get INTO the cell to effect the RNA strands before it can start chopping, and are these not inside the viral structure for the most part??
If this is true then, that Riba has to get inside,
and then on the assumtion all cells are serviced to some degree by the bloodstream,
it means the Riba is getting around,
in which case whether the virus can do cell to cell transfer or not,
what real difference would that make assuming the saturation point of the Riba stays high enough? And, would not this somewhat explain then why the higher dosing seems to yield the more reliable results?
I mean since blood carries the Riba to every cell I'm just not sure the cell to cell replication is really a matter for alarm.
I did wonder a while back, could fat retain virus since it get's less blood supply proportionately,
also wondering could bone matter itself be a hiding place.
but ultimately my main question is, even given a circutous route through the circulation before a Riba molecule reaches a neighboring infected cell let's say,
won't each cell still ultimately get serviced with Riba soon enough....
and if often and long enough in duration then why would it matter so much???
And, isn't that what the SOC is basically now proving out to a greater degree?
Isn't the longer duration tx resulting in people going UND for years now??
ok so that's not just one question....so much for my one time math major!!!!!!
: )))))))))))))))))))))
thanks for pulling this thread up again, I was going crosseyed in the wee hours trying to finish readin it, then and hadn't gotten back to it....people do read, rest assured.
lanier: I can out pain-in-the-neck you anyday of the week
Xquizit: that is what is so crazy. They are saying that Riba stuff goes down better with a lot of fat. So . . . .once you are done with treatment you can sign up for a heart replacement
What a nice thing to know, I only came here I think around May-Aug this year. I have never been on a blog or anything in the chatting, "im" video cam kind of stuff. I was desperate, pitiful and still am in many ways. Yhid forum has helped me. I can vent and try to relatate to others like me. I loved healthcare so much and miss the clinical setting and excitement, but I broke ranks years ago when it comes to Doctors, lawyers or Indian chiefs...lol I was out spoken and asked questions about care plans long before I knew I was afflicted. Now I am a ruthless advocate for people who need to be more proactive with their own health. I wish we all could wake up well, I wish I could see my only child for 30 more years, inside my self awareness tells me it will never happen. I just wish more people could get screened when acute. they have made invto study this past January in a laboratory setting and so I am hopeful for those coming down the pike. It's why I always ask how old people here are? (so rude)
anyway thank you again
regards
Lanier
anyway thank you again
regards
Lanier
Please do not waste your time responding to Mr. Liver, who is also earthman, aka andy and an assortment of fake names. He has very serious issues and has been shunned by other HCV forums.
Please keep an watchful eye on him, as he can be upsetting to people on tx. I enjoyed your informative and was happy to see that you saw right through this nitwit.
Please keep an watchful eye on him, as he can be upsetting to people on tx. I enjoyed your informative and was happy to see that you saw right through this nitwit.
I have trouble with processing in general," Andy, boy do we know that. My God even here you must give these people a hard time. You no nadda on HCV, as you drank all through your tx, and continue to do do. Please get help, contact your local AA.
ROFL. ha! i was thinking of asking HR to marry me but if you are serving hagen das, starbucks, and cherry garcia...maybe i will change my mind.....ahhh are you....
(of course i would have to leave the love of my life for 34 years)
(of course i would have to leave the love of my life for 34 years)
"loading up on saturated fats"
____________________________________
Outrageous! We get to increase the *HDZ factors and the **CG factors!
*Hagen Daz
**Cherry Garcia
____________________________________
Outrageous! We get to increase the *HDZ factors and the **CG factors!
*Hagen Daz
**Cherry Garcia
haha ya, i admit i do get a kick over the "lipid confounding antibody groove"
of course during my tx i did increase intake of fats ( with riba ) and in % TDI. my geno 3a
pre -tx i had a lipid profile done and my LDL were abnormally low causing an alert for cardio vascular disease. this led to a full blown cardiac work up(all negative) and then an interest in dyslipidemia in chronic hcv.
material was hard to come by for this foray because of the lack of research on lipids and hcv.
from my limited understanding i thought that my LDL levels were somehow influenced by the virus perhaps causing the increase risk of steatosis (i did have this on BX). i got confused that othere however had higher levels of lipids with infection which then i assumed were related to diet and perhaps a hereditary influence. after tx my lipids all came back normal with perhaps a need to > HDL's in diet. i do enjoy my handful of almonds and walnuts daily.
the article referenced previously and others discussed the possibility of hcv using the LDL receptor to gain entrance in the cell. (one of many ways for cell entry) HR has it right on that the process of hcv entry into the cell are still not fully understood. i look forward to more coming as you know i am a "lipid nut" lol
back to using HR posts as a study stimulus....hugs HR... hope you are well!
of course during my tx i did increase intake of fats ( with riba ) and in % TDI. my geno 3a
pre -tx i had a lipid profile done and my LDL were abnormally low causing an alert for cardio vascular disease. this led to a full blown cardiac work up(all negative) and then an interest in dyslipidemia in chronic hcv.
material was hard to come by for this foray because of the lack of research on lipids and hcv.
from my limited understanding i thought that my LDL levels were somehow influenced by the virus perhaps causing the increase risk of steatosis (i did have this on BX). i got confused that othere however had higher levels of lipids with infection which then i assumed were related to diet and perhaps a hereditary influence. after tx my lipids all came back normal with perhaps a need to > HDL's in diet. i do enjoy my handful of almonds and walnuts daily.
the article referenced previously and others discussed the possibility of hcv using the LDL receptor to gain entrance in the cell. (one of many ways for cell entry) HR has it right on that the process of hcv entry into the cell are still not fully understood. i look forward to more coming as you know i am a "lipid nut" lol
back to using HR posts as a study stimulus....hugs HR... hope you are well!
MEDICAL PROFESSIONAL
This is of course yet another twist to the HCV-lipid story. Since HCv seems - among other attachment / transfer receptors - to use the LDL receptor as anchoring/plasma membrane translocation enhancing mechanism, the protective effect of high LDL might be correlated to a competitive binding/blocking of that receptor by high LDL levels, reducing reinfection efficacy.
Alternatively, high LDL levels may lead to "overlipidation/lovercoating" of the virions, where their trick starts to backfire, reducing attachment efficiency at the hepatocyte membrane.
Please note that the HCV viral entry mechanims at present are only incompletely understood.
Alternatively, high LDL levels may lead to "overlipidation/lovercoating" of the virions, where their trick starts to backfire, reducing attachment efficiency at the hepatocyte membrane.
Please note that the HCV viral entry mechanims at present are only incompletely understood.
MEDICAL PROFESSIONAL
MerryBe
The virus manages this extremely critical “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.
ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?
1. The antibody binding is already unable to prevent reinfection due to this mentioned feature, together with the constant adaptive evasion by mutation (correctly mentioned by whrose above , but left out in my earlier discussion so as to not further complicate the issue) as part of the viral strategy to escape neutralization. Therefore, even if PPC would add to that " lipid coat" it would not matter. Once you are coated, you are coated.
2. The exact nature of these binding lipds is not known ( at least AFAIK). Chances are that the overall plasam lipid profile would not be altered by PPC so as to enhance this feature, even if it would not alrready have maxed out .
3. There is a small component of neutralizing antibodies in place that seems to have some role in the ability to prevent reinfection in a setting, where there are only a few viruses trying to infect a virgin liver, like in the transplant setting.The HCIG experiments - passive immunization using plasma enriched for HCV antibodies in chimpasnzees- to prevent de novo infection- had a small degree of efficiacy, but not enough to make the difference. But, as mentioned above, Innogenetics in Belgium is currently trying to develop two human monoclonals with the intenion to help prevent reinfection after transplant. I had a discussion in that specific regard with the two lead researchers actually working on this at the Boston meeting, so I am up to speed on that approach.
The virus manages this extremely critical “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.
ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?
1. The antibody binding is already unable to prevent reinfection due to this mentioned feature, together with the constant adaptive evasion by mutation (correctly mentioned by whrose above , but left out in my earlier discussion so as to not further complicate the issue) as part of the viral strategy to escape neutralization. Therefore, even if PPC would add to that " lipid coat" it would not matter. Once you are coated, you are coated.
2. The exact nature of these binding lipds is not known ( at least AFAIK). Chances are that the overall plasam lipid profile would not be altered by PPC so as to enhance this feature, even if it would not alrready have maxed out .
3. There is a small component of neutralizing antibodies in place that seems to have some role in the ability to prevent reinfection in a setting, where there are only a few viruses trying to infect a virgin liver, like in the transplant setting.The HCIG experiments - passive immunization using plasma enriched for HCV antibodies in chimpasnzees- to prevent de novo infection- had a small degree of efficiacy, but not enough to make the difference. But, as mentioned above, Innogenetics in Belgium is currently trying to develop two human monoclonals with the intenion to help prevent reinfection after transplant. I had a discussion in that specific regard with the two lead researchers actually working on this at the Boston meeting, so I am up to speed on that approach.
Since you seem to be getting off on the lipid-confounding-antibody groove, you might find the study referenced below interesting reading. Basically it states that high levels of cholesterol, and specifically high levels of LDL (the "bad" cholesterol) were found to strongly correlate with RVR/EVR and eventual SVR. I actually employed this strategy during my treatment by loading up on the saturated fats prior to treatment and during treatment by eating lots of fattening foods (whole milk, pizza, ice cream etc etc). Can't know if it helped, but based on the strongly correlative LDL->RVR/EVR/SVR data reported in this study, it just mighta!
http://www.natap.org/2006/HCV/080806_02.htm
http://www.natap.org/2006/HCV/080806_02.htm
clarification of above.
it is the proteins on the lipid envelope that attach to circulating lipids. as there are only 2 main envelope proteins on the hcv- E1 and E2. i wonder if both or one has this ability?
it is the proteins on the lipid envelope that attach to circulating lipids. as there are only 2 main envelope proteins on the hcv- E1 and E2. i wonder if both or one has this ability?
as usual as i reread HR comments i find a new gems to explore
your question stimulated this re read. although your inquiry was about PPC in relationship to circulating lipids i found something more remakable from his explanation.
i would guess that PPC has no effect to increase the development of the secondary lipid envelope coat of hcv because 1- PCC composed primarily of polyunsaturated fats actually decrease plasma triglycerides and cholesterol. 2- the addition of polyunsaturated fats in circulating plasma would not have any effect in the ability of the lipid envelope layer of hcv binding to plasma circulating lipids.
will be nice if HR comes in to elaborate! would be nice to clarify if the virus binds circulating HDL's or LDL's in plasma?
but even more remarkable in his explanation was the statement that hcv envelope proteins bind to circulating lipids thus giving it that soft coat that interferes with antibody attachment to the viral epitope. in effect preventing the ability of the antibody from processing the viral epitope and neutralizing it.
wow! i thought antibodies were ineffective because of the envelope proteins E1E2 especially E2(envelope proteins) are hypervariable thus preventing effective antibodies forming due to the constant development of variable epitopes. (the genetic drift causing mutation and development of quasi species cause the hypervariability that are capable of neutralizing antibodies).
i never considered that the lipid layer on the envelope would also prevent antibodies from forming a strong bond to the viral epitope! wow wow. this is the firist time i considered this aspect.
also i never understood the lipid coat to be able to attach more lipids when circulating in plasma. i always thought the bi layer lipid coat was formed from intracellular lipids during the virion maturation inside the cell and by the process of exocytosis. interesting now to realize the viron has the ability to attach circulating lipids in its defense system.
now my coggs are spinning lol!
i came across an interesting article about an emerging science in viral immunotherapy whose focus is to develop agents that will remove the lipid viral coat (delipidation) thus increase viral antigen presentation and processing.
site http://sec.edgar-online.com/2006/03/15/0001047469-06-003438/section2.asp
would love HR to comment on delipidation as a prospect to aid the development of an effective vaccine.
also one of my fav sites on hcv viral biology is
www.natap-org/2001/jun/MoleBio.PDF
i have lots more of such if you are interested
another insight in to the way the virus evades the adaptive (humoral) branch of the immune system!
thanks merry....i enjoy your comments and posts! our understanding is alike a baby compared to HR but perhaps together we babies can reach better understandings of chronic hcv
hugs
your question stimulated this re read. although your inquiry was about PPC in relationship to circulating lipids i found something more remakable from his explanation.
i would guess that PPC has no effect to increase the development of the secondary lipid envelope coat of hcv because 1- PCC composed primarily of polyunsaturated fats actually decrease plasma triglycerides and cholesterol. 2- the addition of polyunsaturated fats in circulating plasma would not have any effect in the ability of the lipid envelope layer of hcv binding to plasma circulating lipids.
will be nice if HR comes in to elaborate! would be nice to clarify if the virus binds circulating HDL's or LDL's in plasma?
but even more remarkable in his explanation was the statement that hcv envelope proteins bind to circulating lipids thus giving it that soft coat that interferes with antibody attachment to the viral epitope. in effect preventing the ability of the antibody from processing the viral epitope and neutralizing it.
wow! i thought antibodies were ineffective because of the envelope proteins E1E2 especially E2(envelope proteins) are hypervariable thus preventing effective antibodies forming due to the constant development of variable epitopes. (the genetic drift causing mutation and development of quasi species cause the hypervariability that are capable of neutralizing antibodies).
i never considered that the lipid layer on the envelope would also prevent antibodies from forming a strong bond to the viral epitope! wow wow. this is the firist time i considered this aspect.
also i never understood the lipid coat to be able to attach more lipids when circulating in plasma. i always thought the bi layer lipid coat was formed from intracellular lipids during the virion maturation inside the cell and by the process of exocytosis. interesting now to realize the viron has the ability to attach circulating lipids in its defense system.
now my coggs are spinning lol!
i came across an interesting article about an emerging science in viral immunotherapy whose focus is to develop agents that will remove the lipid viral coat (delipidation) thus increase viral antigen presentation and processing.
site http://sec.edgar-online.com/2006/03/15/0001047469-06-003438/section2.asp
would love HR to comment on delipidation as a prospect to aid the development of an effective vaccine.
also one of my fav sites on hcv viral biology is
www.natap-org/2001/jun/MoleBio.PDF
i have lots more of such if you are interested
another insight in to the way the virus evades the adaptive (humoral) branch of the immune system!
thanks merry....i enjoy your comments and posts! our understanding is alike a baby compared to HR but perhaps together we babies can reach better understandings of chronic hcv
hugs
All I have to say about your rants is to repost why HepC is called the Dragon.
The liver is represented by a dragon and is said to store anger.
Certainly applies to you
Have a Nice Day
CS
The liver is represented by a dragon and is said to store anger.
Certainly applies to you
Have a Nice Day
CS
sorry this is going to take me a long time to read through,
but a dumb question, regarding thick protein shells you said
>>>>>>>>>>>>>>>The virus manages this extremely critical “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.
ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?
I may be misunderstanding something here, granted, but with my limited knowledge of your lingo, it's kinda hard to be sure if this new info does damage to the PPC equation.
thanks
but a dumb question, regarding thick protein shells you said
>>>>>>>>>>>>>>>The virus manages this extremely critical “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.
ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?
I may be misunderstanding something here, granted, but with my limited knowledge of your lingo, it's kinda hard to be sure if this new info does damage to the PPC equation.
thanks
In the big picutre HCV is not getting it's fair share of dollars. the statement you qoute is out of context. Mr liver and I have been debating this. I never said there was NO research, but I can tell you in the past ten years there were more dollars that is what I am talking about spent of erectile dysfunction than HCV. and since I have no penis I feel like I got the "shaft"
I don't want to argue the point anymore you guys are sold that HCv is just the cats meow when it comes to research so dream on.
I did not mean to offend you, but if I did life goes on for us both it really is no big deal, this is a BLOG
I thought people were "allowed" to share there knowledge and not have to fight for a different idea? I am not right about anything heck I am wrong all the time I am human, I don't want a blue ribbon. I just know what I know from where I have been.
have a nice day go Packers and crown 24 king
Lanier
I don't want to argue the point anymore you guys are sold that HCv is just the cats meow when it comes to research so dream on.
I did not mean to offend you, but if I did life goes on for us both it really is no big deal, this is a BLOG
I thought people were "allowed" to share there knowledge and not have to fight for a different idea? I am not right about anything heck I am wrong all the time I am human, I don't want a blue ribbon. I just know what I know from where I have been.
have a nice day go Packers and crown 24 king
Lanier
"on just about as much as your ridiculous statement of hundreds of pharmacutical companies beating down the doors to research this virus".
I don't understand most of this thread, and probably be no better off if I did. But this comment is unfair. We are very very lucky to have a disease that is common. There is money in this disease, so there is research occuring. If we had some uncommon, as many people do, there is just often not the money to commercialize potential drugs.
I don't understand most of this thread, and probably be no better off if I did. But this comment is unfair. We are very very lucky to have a disease that is common. There is money in this disease, so there is research occuring. If we had some uncommon, as many people do, there is just often not the money to commercialize potential drugs.
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