Aa
HCV difference in life cycle?
Does anyone know why it is possible to cure HCV, but not HIV? It was explained to me as a difference in the virus life cycle, but the explanation given me had some misconceptions that I would like to clarify.
I am not that good at this, but I believe that HIV integrates into the human chromosomal DNA, whereas HCV does not.
Also I think HIV passes the brain/blood barrier, which HCV in most cases does not.
Also I think HIV passes the brain/blood barrier, which HCV in most cases does not.
Life Cycle of HIV, a Retrovirus:
http://www.sumanasinc.com/webcontent/animations/content/lifecyclehiv.html
Life Cycle of Hepatitis C:
http://hopkins-gi.org/multimedia/database/intro_293_VC-04.swf
http://www.sumanasinc.com/webcontent/animations/content/lifecyclehiv.html
Life Cycle of Hepatitis C:
http://hopkins-gi.org/multimedia/database/intro_293_VC-04.swf
"RETROVIRUS
From Wikipedia, the free encyclopedia
A retrovirus is any virus belonging to the viral family Retroviridae. They are enveloped viruses possessing an RNA genome, and replicate via a DNA intermediate. Retroviruses rely on the enzyme reverse transcriptase to perform the reverse transcription of its genome from RNA into DNA, which can then be integrated into the host's genome with an integrase enzyme. The virus then replicates as part of the cell's DNA."
From Wikipedia, the free encyclopedia
A retrovirus is any virus belonging to the viral family Retroviridae. They are enveloped viruses possessing an RNA genome, and replicate via a DNA intermediate. Retroviruses rely on the enzyme reverse transcriptase to perform the reverse transcription of its genome from RNA into DNA, which can then be integrated into the host's genome with an integrase enzyme. The virus then replicates as part of the cell's DNA."
hepatitis C may be easier to treat in some ways than AIDS. That is because H.I.V. turns its RNA into DNA, which is incorporated into the chromosomes of cells it infects, making it hard to totally eliminate the virus. But hepatitis C virus does not do that, and the experience with interferon has shown that if the virus can be eliminated, patients can be cured.
http://query.nytimes.com/gst/fullpage.html?res=9A00E6DF173EF932A25750C0A9659C8B63&sec=health&spon=&pagewanted=all
http://query.nytimes.com/gst/fullpage.html?res=9A00E6DF173EF932A25750C0A9659C8B63&sec=health&spon=&pagewanted=all
Anyone know why interferon and ribavirin cure chronic hep C patients, but not chronic hep B?
Sorry...i cant comment on your question...i did that in another thread and i got the thrid degree...calling me a high jacker...im just going to stick with the topic posted in the thread...
Oh, what the h... Here is a clue for those interested:
"Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process."
"Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process."
Thanks for the input. I still don't see how the protease inhibitors and SOC can eliminate HCV but not HIV or HBV. I understand what you are saying, but not fully the mechanism by which HCV can be blocked from reproducing.
I assume there is something in the HCV life cycle that makes it vulnerable while the other two can find a mechanism that allows it to escape the drugs. HIV is significantly impacted by PIs but somehow finds a way to protect enough virions to keep going and survive long enough to mutate. Anyway, luckily for us this is an academic issue in our case.
I assume there is something in the HCV life cycle that makes it vulnerable while the other two can find a mechanism that allows it to escape the drugs. HIV is significantly impacted by PIs but somehow finds a way to protect enough virions to keep going and survive long enough to mutate. Anyway, luckily for us this is an academic issue in our case.
As I see it the important thing is not that HCV is blocked from reproduction, it is that unlike most viruses HCV is sensitive to an interferon enhanced immune system. The PIs, which block the virus reproduction, can not do the job alone. They only speed up the process, so that the interferon will succeed in its job.
The way I understand viruses is that there is no cure by directly attacking the virus. Our immune system has to do the job. We can make the environment, ie our body, an unpleasant place for the virus, thereby helping the immune system in its effort to kill off the virus, and hopefully the virus will expire. Unfortunately, interferon and ribavirin do not only make the environment unpleasant for the hep C virus, but for us as well. Luckily, we are hardier than the hep C virus.
Also when the virus as with HIV and hep B has become a part of the DNA in the infected cells, I figure each infected cell must die for us to get rid of the disease. Apparently though, a small minority of chronic hep B patients are cured by interferon therapy.
Maybe the fact that HCV does not integrate into the cell DNA is the explanation why interferon works. Because of this HCV might be easier for the interferon enhanced immune system to kill.
Just my 2 cents.
The way I understand viruses is that there is no cure by directly attacking the virus. Our immune system has to do the job. We can make the environment, ie our body, an unpleasant place for the virus, thereby helping the immune system in its effort to kill off the virus, and hopefully the virus will expire. Unfortunately, interferon and ribavirin do not only make the environment unpleasant for the hep C virus, but for us as well. Luckily, we are hardier than the hep C virus.
Also when the virus as with HIV and hep B has become a part of the DNA in the infected cells, I figure each infected cell must die for us to get rid of the disease. Apparently though, a small minority of chronic hep B patients are cured by interferon therapy.
Maybe the fact that HCV does not integrate into the cell DNA is the explanation why interferon works. Because of this HCV might be easier for the interferon enhanced immune system to kill.
Just my 2 cents.
Can one not compare the effect of the PIs as making "everybody's" baseline viral load low and making "everybody" a rapid/quicker responder? No slow responders anymore.
In a nutshell...the PI`s stop the viruus from replcating somewhtt like the RIBA...and the PEG does the killing...BTW...PEG and RIBA were not designed for hepatitis...its just a fluke those drugs work...they wrere initally designed for cancer tx.
"I understand what you are saying, but not fully the mechanism by which HCV can be blocked from reproducing.
I assume there is something in the HCV life cycle that makes it vulnerable"
_________________________
Interferon works in phases. Most of the virus is circulating in your bloodstream. The virus in your blood is the easiest to kill, because it doesn't live as long as the virus that is in liver cells. Also, it is out in the open, so to speak, and not hiding in cells.
The first phase of treatment lasts 1 to 2 days. This phase kills most of the virus circulating in your bloodstream. The action of Interferon in your bloodstream is simple. It mainly slows down the replication of the virus. In order for any life form to survive, it must live long enough to reproduce. By slowing down the rate of replication, the virus dies on its own without producing offspring.
Phase 2 lasts from day 2 through day 14. Interferon is now attacking the virus in your liver cells. This is a slow phase because the virus has trained the liver cells to look as though they aren't infected. The more your viral load drops, the more the interferon is able to see the the infected cells. The Hep C virus has turned the liver cells into virus reproduction factories. It teaches the liver cells how to make more copies of the virus. So now the action of interferon becomes more complicated. Interferon calls for help from other parts of your immune system. These other parts of your immune system degrade the RNA of the virus, interfere with the virus-making process and try to re-teach the liver cells how to behave normally.
Phase 3 lasts from day 14 through day 28, (and continues on through week 24). During this phase, interferon completely switches your immune system into full attack mode. Your immune system can now see which infected liver cells cannot be saved and starts to kill them. Interferon also encourages regeneration of liver cells, so as the infected cells are killed, new cells begin to grow in their place (this is how interferon may help reverse liver damage).
All of this activity takes place within 30 days. That's why your doctor expects to see a 2 log drop in your viral load within 12 weeks of treatment. It means that the interferon is sucessfully working on the virus that is actually in your liver (same with a 4 week RVR).
"I still don't see how the protease inhibitors and SOC can eliminate HCV but not HIV or HBV"
____________________________
The protease of HCV, NS3, is responsible for blocking interferon. That's why protease inhibitors like Telepravir and Boceprevir, are being used for Hep C treatment. They block replication and help interferon.
Co
I assume there is something in the HCV life cycle that makes it vulnerable"
_________________________
Interferon works in phases. Most of the virus is circulating in your bloodstream. The virus in your blood is the easiest to kill, because it doesn't live as long as the virus that is in liver cells. Also, it is out in the open, so to speak, and not hiding in cells.
The first phase of treatment lasts 1 to 2 days. This phase kills most of the virus circulating in your bloodstream. The action of Interferon in your bloodstream is simple. It mainly slows down the replication of the virus. In order for any life form to survive, it must live long enough to reproduce. By slowing down the rate of replication, the virus dies on its own without producing offspring.
Phase 2 lasts from day 2 through day 14. Interferon is now attacking the virus in your liver cells. This is a slow phase because the virus has trained the liver cells to look as though they aren't infected. The more your viral load drops, the more the interferon is able to see the the infected cells. The Hep C virus has turned the liver cells into virus reproduction factories. It teaches the liver cells how to make more copies of the virus. So now the action of interferon becomes more complicated. Interferon calls for help from other parts of your immune system. These other parts of your immune system degrade the RNA of the virus, interfere with the virus-making process and try to re-teach the liver cells how to behave normally.
Phase 3 lasts from day 14 through day 28, (and continues on through week 24). During this phase, interferon completely switches your immune system into full attack mode. Your immune system can now see which infected liver cells cannot be saved and starts to kill them. Interferon also encourages regeneration of liver cells, so as the infected cells are killed, new cells begin to grow in their place (this is how interferon may help reverse liver damage).
All of this activity takes place within 30 days. That's why your doctor expects to see a 2 log drop in your viral load within 12 weeks of treatment. It means that the interferon is sucessfully working on the virus that is actually in your liver (same with a 4 week RVR).
"I still don't see how the protease inhibitors and SOC can eliminate HCV but not HIV or HBV"
____________________________
The protease of HCV, NS3, is responsible for blocking interferon. That's why protease inhibitors like Telepravir and Boceprevir, are being used for Hep C treatment. They block replication and help interferon.
Co
"Can one not compare the effect of the PIs as making "everybody's" baseline viral load low and making "everybody" a rapid/quicker responder? No slow responders anymore. "
---------------------------------
I suppose you can say that. But the PI's kill the wild type virus (which is the much larger number). You still need the interferon to kill the mutant type virus. And if somebody is interferon resistant, it's not going to work even if the PI lowered the viral load.
Co
---------------------------------
I suppose you can say that. But the PI's kill the wild type virus (which is the much larger number). You still need the interferon to kill the mutant type virus. And if somebody is interferon resistant, it's not going to work even if the PI lowered the viral load.
Co
"The virus in your blood is the easiest to kill, because it doesn't live as long as the virus that is in liver cells."
Is this true? I thought an HCV copy was extremely short lived anyway. But that blood cells regenerate in 4 weeks, whereas liver cells regenerate in 300-500 days.
Do you have a link to what you stated in your post? It would be interesting to read the original link.
Is this true? I thought an HCV copy was extremely short lived anyway. But that blood cells regenerate in 4 weeks, whereas liver cells regenerate in 300-500 days.
Do you have a link to what you stated in your post? It would be interesting to read the original link.
With all due respect.... we may have to re-define what we mean when we call people "non-responders". It appears that non-responders do indeed respond to Telaprevir triple therapy . Willy
-------------------------------------------------------------------
http://www.hivandhepatitis.com/2008icr/aasld/docs/111108_a.html
Prove 3 results reported at AASLD 2008 (from 453 genotype 1 ----past TX failures)
"Based on these findings, the investigators stated, "In a population of patients who have failed previous [pegylated interferon/ribavirin] treatment, response rates 12 weeks after end of treatment were 52% overall in the T12/PR 24 arm: 73% in prior relapsers, 41% in prior non-responders."
(These were SVR 12 results and therefore not "official"-- Willy)
-------------------------------------------------------------------
http://www.hivandhepatitis.com/2008icr/aasld/docs/111108_a.html
Prove 3 results reported at AASLD 2008 (from 453 genotype 1 ----past TX failures)
"Based on these findings, the investigators stated, "In a population of patients who have failed previous [pegylated interferon/ribavirin] treatment, response rates 12 weeks after end of treatment were 52% overall in the T12/PR 24 arm: 73% in prior relapsers, 41% in prior non-responders."
(These were SVR 12 results and therefore not "official"-- Willy)
Non-responders does not tell us if we can do without response to SOC. Null responders does.
"With all due respect.... we may have to re-define what we mean when we call people "non-responders". "
----------------------------------
Nowhere in my posts did I say, "non-responders". I said "interferon resistant".
"It appears that non-responders do indeed respond to Telaprevir triple therapy"
-----------------------------------
But were they null responders, or were they "non-responders" because they were under-dosed, their dose was reduced or interrupted, etc?
Co
----------------------------------
Nowhere in my posts did I say, "non-responders". I said "interferon resistant".
"It appears that non-responders do indeed respond to Telaprevir triple therapy"
-----------------------------------
But were they null responders, or were they "non-responders" because they were under-dosed, their dose was reduced or interrupted, etc?
Co
"Also I think HIV passes the brain/blood barrier, which HCV in most cases does not."
--------------------------------------
HCV RNA negative strand, which shows replication, was found in the brain tissue of 3 out of 12 Hep C patients in this study.
According to the prevailing hypothesis, circulating lymphocytes cross the blood-brain barrier carrying HCV to the central nervous system ...and the virus is then replicated in the macrophages and microglia in the brain as a separate compartment.
HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS.
Wilkinson J, Radkowski M, Laskus T.
St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Institute of Infectious Diseases, Warsaw Medical University, Warsaw, Poland.
Hepatitis C virus (HCV) infection is often associated with cognitive dysfunction and depression. HCV sequences and replicative forms were detected in autopsy brain tissue and cerebrospinal fluid from infected patients suggesting direct neuroinvasion. However, the phenotype of cells harboring HCV in brain remains unclear. We studied autopsy brain tissue from 12 HCV-infected patients, 6 of these patients were coinfected with HIV. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (CD68), oligodendrocytes (CNPase), astrocytes (GFAP) and neurons (NeuN), separated by laser capture microscopy (LCM) and tested for the presence of positive and negative strand HCV RNA. Sections were also stained with antibodies to viral nonstructural protein 3 (NS3), separated by LCM and phenotyped by real-time PCR. Finally, sections were also double stained with antibodies specific for cell phenotype and HCV NS3. HCV RNA was detected in CD68-positive cells in 8 patients and negative strand HCV RNA, which is a viral replicative form, was found in 3 of these patients. HCV RNA was also found in astrocytes from 3 patients, but negative strand RNA was not detected in these cells. In double immunostaining, 83%-95% of cells positive for HCV NS3 were also CD68-positive, while 4% to 29% were GFAP-positive. NS3-positive cells were negative for neuron and oligodendrocyte phenotypic markers. In conclusion, HCV infects brain microglia/macrophages and to a lesser extent astrocytes. Our findings could explain the biological basis of neurocognitive abnormalities in HCV infection.
http://www.ncbi.nlm.nih.gov/pubmed/19019968?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel
Co
P.S. Things that cause deterioration of the blood-brain barrier and might make it easier for HCV to cross it......high blood pressure, microwaves and HIV. But I can't remember where I read that.
--------------------------------------
HCV RNA negative strand, which shows replication, was found in the brain tissue of 3 out of 12 Hep C patients in this study.
According to the prevailing hypothesis, circulating lymphocytes cross the blood-brain barrier carrying HCV to the central nervous system ...and the virus is then replicated in the macrophages and microglia in the brain as a separate compartment.
HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS.
Wilkinson J, Radkowski M, Laskus T.
St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Institute of Infectious Diseases, Warsaw Medical University, Warsaw, Poland.
Hepatitis C virus (HCV) infection is often associated with cognitive dysfunction and depression. HCV sequences and replicative forms were detected in autopsy brain tissue and cerebrospinal fluid from infected patients suggesting direct neuroinvasion. However, the phenotype of cells harboring HCV in brain remains unclear. We studied autopsy brain tissue from 12 HCV-infected patients, 6 of these patients were coinfected with HIV. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (CD68), oligodendrocytes (CNPase), astrocytes (GFAP) and neurons (NeuN), separated by laser capture microscopy (LCM) and tested for the presence of positive and negative strand HCV RNA. Sections were also stained with antibodies to viral nonstructural protein 3 (NS3), separated by LCM and phenotyped by real-time PCR. Finally, sections were also double stained with antibodies specific for cell phenotype and HCV NS3. HCV RNA was detected in CD68-positive cells in 8 patients and negative strand HCV RNA, which is a viral replicative form, was found in 3 of these patients. HCV RNA was also found in astrocytes from 3 patients, but negative strand RNA was not detected in these cells. In double immunostaining, 83%-95% of cells positive for HCV NS3 were also CD68-positive, while 4% to 29% were GFAP-positive. NS3-positive cells were negative for neuron and oligodendrocyte phenotypic markers. In conclusion, HCV infects brain microglia/macrophages and to a lesser extent astrocytes. Our findings could explain the biological basis of neurocognitive abnormalities in HCV infection.
http://www.ncbi.nlm.nih.gov/pubmed/19019968?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel
Co
P.S. Things that cause deterioration of the blood-brain barrier and might make it easier for HCV to cross it......high blood pressure, microwaves and HIV. But I can't remember where I read that.
HIV can be inhibited as long as long as patients are put on a certain drug (forgot the name i learned in bio). the drug can even reduce the virus to UND for HIV, however, once the patient is off the drug, HIV returns bc my professor said it can hide during tx.
i asked my hepa about relapsed for HCV after tx, and she told me that relapse happens when people are reinfected. didn't mention anything about virus return from hiding in the body.
i asked my hepa about relapsed for HCV after tx, and she told me that relapse happens when people are reinfected. didn't mention anything about virus return from hiding in the body.
Co:
"But were they null responders, or were they "non-responders" because they were under-dosed, their dose was reduced or interrupted, etc?"
------------------------------------------------------
We will soon see, or at least better see. In the past it was virtually impossible to know exactly how and why people failed. Unless one had meticulous records of weekly viral loads, dosing records, etc it was a matter of supposition.
When the people who failed Prove 1 and Prove 2 (the SOC control arm "failures"; all geno 1 naives) were given the opportunity to be placed into rollover arms in which they were given triple therapy. We will be able to see all the classic groups of treatment failures (from null responder to relapsers) respond when given triple therapy. When they classify a person a null responder they will have fairly detailed records to prove it. It will then be followed up with detailed response rates to triple therapy given to the exact same people who had prior failed SOC.
Given the response rates of Prove 3 with past treatment failures I am hopeful that we will see null responders be converted into responders and perhaps even SVR success stories.
I am not trying to argue the point about interferon resistance but I would like to open up the possibility that even so called "null or non response" to SOC does not mean that one may not be able to be cured using protease or polymerase inhibitors (in conjunction with IFN & RBV) I think sometimes people attribute null response to interferon resistance. (I understand that presumably all interferon resistant people will be null responders (to current SOC) but that not all null responders are therefore interferon resistant. Does that sound right to you?)
I see that Rocker posted an article in which (it was claimed) that a Sherring-Plough 2nd generation PI in development was said to be 10X more powerful (in vitro) than existing PI's.(meaning Telaprevir and Boceprevir, presumably)
At some point the inhibitors may become effective enough that interferon (or RBV) will be dropped from treatment. That day may be here sooner than we think. Trials for such treatments may soon start several pharma's. Vertex had one planned on in 2009 I believe
By the way..... Vertex (well, actually Tibotech) will have a European trial which will utilize the SOC "lead in" before dosing Telaprevir on past treatment failures, null responders included. Figure over 18 months to get the trial started, dosed for a year and a 6 month wait for an "official" SVR PCR.
http://www.hivandhepatitis.com/hep_c/news/2008/102408_b.html
best,
Willy
"But were they null responders, or were they "non-responders" because they were under-dosed, their dose was reduced or interrupted, etc?"
------------------------------------------------------
We will soon see, or at least better see. In the past it was virtually impossible to know exactly how and why people failed. Unless one had meticulous records of weekly viral loads, dosing records, etc it was a matter of supposition.
When the people who failed Prove 1 and Prove 2 (the SOC control arm "failures"; all geno 1 naives) were given the opportunity to be placed into rollover arms in which they were given triple therapy. We will be able to see all the classic groups of treatment failures (from null responder to relapsers) respond when given triple therapy. When they classify a person a null responder they will have fairly detailed records to prove it. It will then be followed up with detailed response rates to triple therapy given to the exact same people who had prior failed SOC.
Given the response rates of Prove 3 with past treatment failures I am hopeful that we will see null responders be converted into responders and perhaps even SVR success stories.
I am not trying to argue the point about interferon resistance but I would like to open up the possibility that even so called "null or non response" to SOC does not mean that one may not be able to be cured using protease or polymerase inhibitors (in conjunction with IFN & RBV) I think sometimes people attribute null response to interferon resistance. (I understand that presumably all interferon resistant people will be null responders (to current SOC) but that not all null responders are therefore interferon resistant. Does that sound right to you?)
I see that Rocker posted an article in which (it was claimed) that a Sherring-Plough 2nd generation PI in development was said to be 10X more powerful (in vitro) than existing PI's.(meaning Telaprevir and Boceprevir, presumably)
At some point the inhibitors may become effective enough that interferon (or RBV) will be dropped from treatment. That day may be here sooner than we think. Trials for such treatments may soon start several pharma's. Vertex had one planned on in 2009 I believe
By the way..... Vertex (well, actually Tibotech) will have a European trial which will utilize the SOC "lead in" before dosing Telaprevir on past treatment failures, null responders included. Figure over 18 months to get the trial started, dosed for a year and a 6 month wait for an "official" SVR PCR.
http://www.hivandhepatitis.com/hep_c/news/2008/102408_b.html
best,
Willy
Reason why we are behind in a more effective cure for hepatitis is because all the research funds in the past have pumped into cancer cures ,,,(which there is none and will never be)..cancer is caused by the chemicals in our food and water...also all the cash went to AIDS cures.....its about time the new PI`s are on the way...
Sorry for posting on youir thread..
I AM NOT A HIGH JACKER
Sorry for posting on youir thread..
I AM NOT A HIGH JACKER
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.
