Hepatitis C Community
I'm confused...
About This Community:

This forum is for questions about medical issues and research aspects of Hepatitis C such as, questions about being newly diagnosed, questions about current treatments, information and participation in discussions about research studies and clinical trials related to Hepatitis. If you would like to communicate with other people who have been touched by Hepatitis, please visit our new Hepatitis Social/Living with Hepatitis forum

Font Size:
A
A
A
Background:
Blank
Blank
Blank
Blank Blank

I'm confused...

Hi everyone,
I've been thinking how exactly INF works in the body. There is an opinion I read on the board which implies that INF boosts the immune system and helps to fight the virus off. On the other hand, I came across the article on www.pegasys.com . It turns out that our immune system fights INF?!?
-----
To help interferon last longer in the body, science has turned to a process called "pegylation." Through pegylation, a special strand (commonly called a PEG) is attached to the interferon molecule. Once attached, the PEG helps protect the interferon from being destroyed by your immune system. As a result, interferon that has a PEG can last longer in the body. This added time in the body improves the chances that alpha interferon will reach and kill hepatitis C-infected cells.
-----
I'm confused!

Also, can someone explain how Ribavirin is working? I read somewhere that it actually makes the virus mutate at a very high rate and in this process virus 'loses' its genetic information making it harmless??? ( so called "genetic meltdown" )
At least this explains why monotherapy with Ribavirin alone will not get rid of the virus, but will it prevent the virus from damaging the liver?!?

Thank you for your kind support!
Related Discussions
16 Comments Post a Comment
Blank
Avatar_n_tn
interferons are a family of proteins that occur naturally in the body and are part of our defense against viral infection. As part of our anti-viral defense mechanism, higher quantities of interferons are produced. They don't directly do anything to the virus but act as a kind of Paul Revere: they bind to cell surfaces and trigger a complex response whereby cells start to produce higher quantities of "intruder-alert" proteins. One of the genes whose expression is induced by interferon is PKR, a protein that explicitly inhibits viral replication.

Taking our IFN shots is a bit like taking a vitamin supplement - we are taking more of something that the body makes naturally. In the case of the peg-IFN, as you point out, the naturally occurring protein has been modified by addition of an auxiliary molecule, the "peg". The point of attaching this big cannonball to the IFN is just to keep the Paul Revere effect going longer. Normally the body breaks down and recycles proteins fairly quickly - the peg-IFN hangs  around longer, so we don't need to inject it as often.

The anti-viral effect of all this extra IFN is well documented : within 24 hours of the first shot it is common to observe a 1/10 reduction in the amount of free virus floating around in the blood stream of responders.

This is complicated by the fact that the virus has its own strategies for shutting down the alarm: some HCV proteins interact with PKR and slow down its activation by IFN (think of slipping the guards a little ambien so they won't hear Paul Revere when he comes around).

Ribavirin is another story. If you compare your high-school bio book with your ribavirin medication guide you'll see the drug looks very much like either an C or a T nucleotide (  that is, ribose attached to something that resembles a pyrimidine). So ribavirin is a small molecule that looks a lot like the building blocks of our DNA chains - hence the name "nucleoside analog".

Three mechanisms of anti-viral action for riba have been <a href="http://www.springerlink.com/app/home/content.asp?wasp=pe669ujuwlckyw53xxb0&referrer=contribution&format=2&page=1&pagecount=10">investigated</a>. The details get pretty involved, but one of the leading candidates is the proposal that the medicine increases the virus's mutation rate to the point where it's no longer viable. That is instead of picking up a C or a T when duplicating the virus' RNA, the virus' polymerase (the molecule that does the copying) picks up a riba molecule instead leading to mistakes down the road. HCV like to live on the wild side as far as mutation frequency goes (changing quickly is one of its strategies for success) and its polymerase  includes no error-checking. The extra level of error induced by the riba is thought to push the virus over the edge (error catastrophe or meltdown).  You might ask yourself if the riba can induce errors in virus replication why can't it induce errors in my own DNA. This is not a great question to ask yourself - but remember that unlike the virus, our polymerase does include an error-checking feature...

This story goes on and on : the interaction of the virus with our immune response is much more involved that its interaction with the meds. I must confess I'm getting  obsessed with it.
There is an important practical side to all this however.

None of these drug mechanisms are in any way specific to the virus. I assume this is what mickeymike is referring to when he says current therapy is "a blunt instrument". It's not quite surgery with a chain saw but it leaves a lot to be desired. Part of the reason for the noxious sides is that we're mucking with very general underlying phenomena rather than targeting the virus itself. This is changing - we now have crystal structures for several of the HCV proteins (in best Clint Eastwood voice : "I know where you live punk!") and it's very reasonable to expect better drugs to follow.

Blank
Avatar_n_tn
Thanks for the tidy lesson in combo-therapy kinetics.
Blank
Avatar_n_tn
Hi MAD, this gives me a chance to thank you  for your very incisive comments - you have a gift for getting at the heart of an issue.
Blank
Avatar_n_tn
Great!!! Good reading.  Thanks for the info. I will print it and keep it since I will surely have to read it a couple times for it to sink in. LL
Blank
Avatar_n_tn
Like Lori said, Wow!  What a great explanation.  Thank you so much.
Blank
Avatar_n_tn
Damn!  There are some really bright people here. "Willing," thanks for breaking it down. I still had to read it twice! Aloha
Blank
Avatar_n_tn
Thanks so much for clearing things up:) That was great!
Blank
Avatar_n_tn
A, B, C, F, X..........  Do you seriously expect that anyone here could tell the difference?  LOL!!
Blank
Avatar_n_tn
this group is so supportive, it's great to be able to give something back ( like any typical techno-geek, my social skills are comparable to those of a large kitchen appliance, but hell even a 'fridge needs defrosting). Also, it wouldn't be called brain fog without a reason : a riba molecule is actually incorporated during hcv replication  as a G or A analog, not C or T as I wrote above.
Blank
Avatar_n_tn
That was a terrific explanation!  Thanks.  M.N.
Blank
Avatar_f_tn
That was an absolutly wonderful explanation. I printed it to show my doctor's office Thanks !
Blank
Avatar_n_tn
Thank you for that great explanation. Reading that makes me even more amazed that so many people can clear this virus with these drugs!

Kathy
Blank
Avatar_n_tn
Um...all of the sudden...I feel really...STUPID!  

Holy ****!  

I have a Physicist friend in France that studied Electomagnetic fields and when she tries to explain her experiments to me I sometimes feel like maybe I should do K-College again.  I just sit there with a blank face...rocking...drooling...feeling the last two brain cells dying off trying to make some sense....

...I kinda felt the same way when I read your post.

Holy ****!  Great Info!

Here is a piece of my friends work http://arxiv.org/abs/cond-mat/0012077
Blank
30678_tn?1217992847
ill tell u what my Dr told me about the way the pegasyst and ribvirin works, the pegasyst (interferon) keeps the virus from entering the cells because once they are in they are safe to do the nasty...but they mutate fast and are short lived. the ribavirin helps kill the virus...but can only get to them outside the cell...hence the the names pegasyst and co pegus as they work together as a team to kill the dragon. may be a simple explanation but it works for me
Blank
Avatar_n_tn
I'm one of those "wow" people.  I kept reading and reading and thought I could keep up with you...but I'm not sure I did.  Post MORE.  You are quite obviously well-versed in the virus mechanism.  Are YOU OK?
Blank
Avatar_n_tn
Hi, I appreciate your asking. I'm doing fine thanks. Hard to admit, but sometimes this brain fgog can be downright pleasant. Hope you are well.
Blank
Post a Comment
To
Blank
Weight Tracker
Weight Tracker
Start Tracking Now
Hepatitis C Community Resources
RSS Expert Activity
242532_tn?1269553979
Blank
How to Silence Your Inner Critic an...
Apr 16 by Roger Gould, M.D.Blank
242532_tn?1269553979
Blank
Emotional Eaters: How to Silence Yo...
Mar 26 by Roger Gould, M.D.Blank
1344197_tn?1392822771
Blank
Vaginal vs. Laparoscopic Hysterecto...
Feb 19 by J. Kyle Mathews, MD, DVMBlank
Top Hepatitis Answerers
1747881_tn?1358189534
Blank
hrsepwrguy
Greeley, CO
317787_tn?1373214989
Blank
Dee1956
DC
446474_tn?1385271190
Blank
HectorSF
CA
Avatar_m_tn
Blank
copyman
1815939_tn?1377995399
Blank
pooh55811
96938_tn?1189803458
Blank
FlGuy
South, FL