Replies to post #67039 on Biotech Values

[iwfal]

What does somewhat invisible mean?

Ok, a reasonable response in that 'somewhat' was a cop out on my part. I inserted the adjective because although the paper says that the hcv is tuned to evade the immune system obviously something is limiting the growth of the virus. I do not know what that is - maybe it is a partially effective immune system? Maybe a hcv resource issue... ?

That lack of information does indicate a potential hole in my argument - but as I said I'd be the last person to make a do or die stand based upon MoA arguments, precisely because there is always something you don't understand.

That said, your argument, which is that it is largely about numbers (and so not about immune tollerance) has a similar hole - why doesn't the hcv run rampant once it gets to large numbers?

If a normal immune system can kill the HCV virions as fast as the virions are reproduced.

I've seen nothing to indicate this is how the immune system and HCV work. On the contrary the whole point of that paper was that HCV modifies itself to be invisible. Whether this invisibility is all or nothing is not clear to me - but I sure wouldn't count on small numbers being controlled by the immune system if there is some invisibility cloak. But OTOH maybe they will be controlled by something else - e.g. the random chance of getting to another susceptible cell to reproduce.

Also note the viral rebound in the phase 1 trials of HCV drugs indicates even when knocked down a lot (2.7 logs is a lot in a shear percentage basis) the immune system can't keep them down. (I'll concede that there may be other factors at play here - so like all MOA arguments it needs to be tempered with caution.)

[ThomasS]

HCV: "If a normal immune system can kill the HCV virions as fast as the virions are reproduced, thereby keeping the viral load at an extremely low level, the patient is effectively cured, barring degradation to the patient’s immune system from something unrelated to the HCV infection. From a practical standpoint, holding the virus at such a low level is as good as total eradication of the virus for almost all patients."

Spot on, although I would add a caveat: A given viral load level affects each patient differently for a myriad of reasons. To wit: My average load is quite "high" by traditional measures; yet, my liver enzymes are only mildly elevated. (The traditional hallmark of continuing damage to hepatocytes).
Coffee consumption is just one of many suspects for my viral tolerance/protective liver effects.