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.
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?!?
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.
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.
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
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
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?
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