Aa
The HCV Family tree and what it tells the researchers about the various genotypes and their resistance to immune response.
In this study one goal of the authors was to determine which genotypes are the oldest and which are the youngest in an effort to explain the different response rates seen in treatment and resolved acute infections. They created a phylogenetic "family tree" to illustrate the evolution of genotypes according to their relative ages. Their hypothesis was the older the genotype the less resistance it would display which in turn was based on the assumption that HCV genotypes owe some of their evolution over time through immune selective pressures.
One example of virus evolution that can affect disease course is found in the area of signaling between cells. One of these chemical signals used by our cells results in the production of PKR , an enzyme. PKR has the ability to shut down proteins in infected cells which are needed for the viral replication process. Over time the genotypes have developed different abilities in this area which the authors predicted should occur according to their age. The newer genos have a more robust ability in this area---as well as in some others, of course.
And they answer the age-old question : "If geno 2 is one of the oldest why hasn't it continued to evolve into the toughest to treat? Why did this geno stop evolving at a spot where it is more susceptible to the host immune responses and can be eliminated in the acute stage easier than other genos ?" This study does a good job in explaining this and other reasons behind the differences seen in viral/host responses and genotype. --- ML
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006579#pone-0006579-g004
--ML
One example of virus evolution that can affect disease course is found in the area of signaling between cells. One of these chemical signals used by our cells results in the production of PKR , an enzyme. PKR has the ability to shut down proteins in infected cells which are needed for the viral replication process. Over time the genotypes have developed different abilities in this area which the authors predicted should occur according to their age. The newer genos have a more robust ability in this area---as well as in some others, of course.
And they answer the age-old question : "If geno 2 is one of the oldest why hasn't it continued to evolve into the toughest to treat? Why did this geno stop evolving at a spot where it is more susceptible to the host immune responses and can be eliminated in the acute stage easier than other genos ?" This study does a good job in explaining this and other reasons behind the differences seen in viral/host responses and genotype. --- ML
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006579#pone-0006579-g004
--ML
Hi Mr. Liver,
Thank you for your reply.
Though studies such as this can be tough for me to slog through, I agree with the others that it's a really excellent and fascinating read. I had to find my better reading glasses, though.
Yes, you're correct that my last question was about how migration patterns would affect distribution of genos and their subtypes. I was mainly wondering aloud.
Interesting how geno 6 is now parked between geno 3 and 2 in terms of success rates.
And fascinating that thirty days would be sufficient to SVR in the rare circumstance of hitting it with SOC within a month of infection. HCIT ('how cool is that')!
The numbers for HCV and HBV in China are staggering, over 40 million and eighty million respectively. One in ten, and/or. That's hard to imagine how that will evolve.
Best regards,
Susan
Thank you for your reply.
Though studies such as this can be tough for me to slog through, I agree with the others that it's a really excellent and fascinating read. I had to find my better reading glasses, though.
Yes, you're correct that my last question was about how migration patterns would affect distribution of genos and their subtypes. I was mainly wondering aloud.
Interesting how geno 6 is now parked between geno 3 and 2 in terms of success rates.
And fascinating that thirty days would be sufficient to SVR in the rare circumstance of hitting it with SOC within a month of infection. HCIT ('how cool is that')!
The numbers for HCV and HBV in China are staggering, over 40 million and eighty million respectively. One in ten, and/or. That's hard to imagine how that will evolve.
Best regards,
Susan
Enjoyed it. Favorited it.
It's right up there with:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847443/?tool=pubmed
and
http://vir.sgmjournals.org/cgi/content/full/85/11/3173
Don't know if the way they had to fiddle their numbers to make their samplings fit qualifies as "thorough in methodology".
But then, I don't know much.
It's right up there with:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847443/?tool=pubmed
and
http://vir.sgmjournals.org/cgi/content/full/85/11/3173
Don't know if the way they had to fiddle their numbers to make their samplings fit qualifies as "thorough in methodology".
But then, I don't know much.
Hi Portann,
The steep viral decline in the first 72 hours of the first IFN shot is usually over 90% for all genotypes. In a study I read long ago it was shown that if someone could identify a a time point where there was a strong possiblity of HCV infection and then treated within one month for 30 days the SVR rate was 100% regardless of genotype. Save for the healthcare professionals, penal system employees, and first responders there probably aren't too many who can pinpoint in real time when an HCV infection occurs so this window of oppty passes unknown for most of us with it.
In the study, with the aid of a supercomputer they were able to accurately predict the IFN resistance profile of G5 and G6 and it was demonstrated with an accuarcy approaching100% . HBV is the biggest health threat in all of SE Asia, with high mortality rates in Indochina, and the Oriental countries as well. Don't forget the Chinese where appx 41 million are infected with HCV and over 80 mllion with HBV. In China about 80% are either geno 1b or 2a. I did read one paper where researchers found 3 cities in China where geno 6 has replaced G2 as the second most prevalent strain. But, again HBV is their biggest health threat in China, also. Its hard to imagine but almost 1 in 10 ppl in China's 1.3 billion have either HBV, and/or HCV. I guess those ancient Chinese herbs are just not up to the task. ;)
The phylogenetic tree was used to graphically display the evolution of the HCV genome over time and determine the age of major genotypes. They found when genos were listed by age and then compared to IFN resistant profiles there was a strong correlation. This is the list in the order of most IFN resistant genotypes to the least: 1,4,5,3,6,2. Am I correct that your last question is about the transient nature of the world's population and how it could affect distribution of genos and their subtypes ? Do I have this right ?Thanks for the post.
Regards, ML
what is HCIT ?
The steep viral decline in the first 72 hours of the first IFN shot is usually over 90% for all genotypes. In a study I read long ago it was shown that if someone could identify a a time point where there was a strong possiblity of HCV infection and then treated within one month for 30 days the SVR rate was 100% regardless of genotype. Save for the healthcare professionals, penal system employees, and first responders there probably aren't too many who can pinpoint in real time when an HCV infection occurs so this window of oppty passes unknown for most of us with it.
In the study, with the aid of a supercomputer they were able to accurately predict the IFN resistance profile of G5 and G6 and it was demonstrated with an accuarcy approaching100% . HBV is the biggest health threat in all of SE Asia, with high mortality rates in Indochina, and the Oriental countries as well. Don't forget the Chinese where appx 41 million are infected with HCV and over 80 mllion with HBV. In China about 80% are either geno 1b or 2a. I did read one paper where researchers found 3 cities in China where geno 6 has replaced G2 as the second most prevalent strain. But, again HBV is their biggest health threat in China, also. Its hard to imagine but almost 1 in 10 ppl in China's 1.3 billion have either HBV, and/or HCV. I guess those ancient Chinese herbs are just not up to the task. ;)
The phylogenetic tree was used to graphically display the evolution of the HCV genome over time and determine the age of major genotypes. They found when genos were listed by age and then compared to IFN resistant profiles there was a strong correlation. This is the list in the order of most IFN resistant genotypes to the least: 1,4,5,3,6,2. Am I correct that your last question is about the transient nature of the world's population and how it could affect distribution of genos and their subtypes ? Do I have this right ?Thanks for the post.
Regards, ML
what is HCIT ?
"You're up to three stars there Mr. Liver. Grats. >.<
Yes, I noticed that. That was so easy I'll be up to 8 or 9 by the end of the month .
I'm glad you enjoyed the article. I found it to be very thorough in methodology and references which is what I look for in a good study.
ML
Yes, I noticed that. That was so easy I'll be up to 8 or 9 by the end of the month .
I'm glad you enjoyed the article. I found it to be very thorough in methodology and references which is what I look for in a good study.
ML
You're up to three stars there Mr. Liver. Grats. >.<
Thanks for the article, excellent read.
Thanks for the article, excellent read.
Browsing through this definitely made my head spin and it's over my head as well but two things popped out at me that were incidental to the point of the study.
One was its assumption that G4 is easier to treat than G1; I recall Bali (a G4) asking about info for his genotype and there didn't seem to be much around to reassure him. Interesting that the study stated as a hard fact that G4's are easier to treat than G1's.
The other matter mentioned that I hadn't been aware of is that all genotypes, regardless of ease or difficulty in treating during the chronic stage, respond equally well to interferon in the acute stage. Didn't know that.
The incidence of G5 could be astronomical and I wonder how this can ever be managed economically in Southeast Asia. Vietnam (G5?) currently has the highest incidence of HCV in the world, surpassing Egypt (G4). Even simple sterilization methods like autoclaving in dental offices are very expensive. So although HCV may be on the decline in some areas of the world, it may be the opposite elsewhere. And how does the tree work, given the unprecedented mobility of populations from one area of the world to another?
You are so much smarter than I am, too, only I always knew that! Thanks for posting.
HCIT,
Susan
One was its assumption that G4 is easier to treat than G1; I recall Bali (a G4) asking about info for his genotype and there didn't seem to be much around to reassure him. Interesting that the study stated as a hard fact that G4's are easier to treat than G1's.
The other matter mentioned that I hadn't been aware of is that all genotypes, regardless of ease or difficulty in treating during the chronic stage, respond equally well to interferon in the acute stage. Didn't know that.
The incidence of G5 could be astronomical and I wonder how this can ever be managed economically in Southeast Asia. Vietnam (G5?) currently has the highest incidence of HCV in the world, surpassing Egypt (G4). Even simple sterilization methods like autoclaving in dental offices are very expensive. So although HCV may be on the decline in some areas of the world, it may be the opposite elsewhere. And how does the tree work, given the unprecedented mobility of populations from one area of the world to another?
You are so much smarter than I am, too, only I always knew that! Thanks for posting.
HCIT,
Susan
I tried to read it I really did but boy Mr. L you are so much smarter than I all the jargon gets to me after a while. But I get the jist and that's all that really matters to me anyway.
Very interesting stuff........even if it is over my head! Thanks!
Very interesting stuff........even if it is over my head! Thanks!
It actually did make my head spin around a lot. :-)
I'm still fighting against my interferon brain :-(
I'm still fighting against my interferon brain :-(
I'm glad you found it informative as I did. Plus, I actually could read the paper without getting a headache and glassy eyes, a welcome change from the usual studies which require a medical dictionary for me to get through them.
Regards,ML
Regards,ML
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