HCV difference in life cycle?

[Andiamo1]

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.

[CoWriter]

"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. "
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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

[CoWriter]

"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"
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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"
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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

[Rockerforlife]

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.

[zazza]

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.

[zazza]

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.

[Andiamo1]

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.