My understanding of the term “wild type” virus is to distinguish it from “variant” or “mutant” virus. I suppose an example with HCV could be a patient that is treatment naïve would be considered infected with Wild Type virus, versus the patient that has unsuccessfully treated, creating escape variants/mutants.
Although I believe this is the distinction, I’m *far* from a microbiologist, lol. Maybe Willing or someone else will stop by to confirm or rebuke?
I’ve been following your saga, BTW; I really don’t have much info on GT-4, much less acute HCV. I treat with CPMC as well here in Sacramento, and although I’m quite satisfied with my care, I’m not a particularly complicated patient. Due to the complexities of you individual case, I’d think that an additional consult would be de rigueur. In fact, you might want to consider asking CPMC for a referral? I think it adds up to good medicine for all parties involved.
Take care, and keep us posted as to your progress—
Bill thanks for the comment about my saga......I TRULY do hate to be a drama queen but sometimes this damn disease....well you know what i mean. I got the phone number for Schiff in Miami and am attempting to get a phone consult with him. I'll talk with my tx team about it on Thursday (appt. changed from Mon) as well.
Jim, you crack me up. Believe it or not, my wild phase was short (19-22) and not that wild....it was in Wisconsin, of all places! So it was pretty much limited to much mother's milk (beer) and a little bit of what we called "weed". Then I started popping kids and cleaned up my act and some baby butts as an avocation. But that was funny, dude.
I'm sure some will disagree on this, but I always tried to keep my big-shot HCV docs at arm length when getting a consult. In other words, I collected all my records, and then made the appointment myself with the consult and did not necessarily mention it to my treatment doc. My reasoning was that by keep them at arm's length I would tend to get a more objective second (or third) opinion as opposed to one doc calling another, whom he probably knows. Also felt my tx docs ego would be less brusied this way. May be wrong on this but that's how I proceeded with my several consults during tx.
There are 11 known (6 major known) species - then subtypes...
I'm thinking wildtype might be a variant on a strain - but that has mutated to an undistinguishable F-Z type.
1a goes up to 1b, 1c, etc.
4a, b, c ----
ad infinitum --- but only a few have been identified.
Or it could be a mutant combo.
I'm thinking - that it's possible to be infected double - for example - you have 1a - get surgery with a dirty instrument with someone who has 1b --- and now you have both running through your system - and it's now a wild-type... They can't confirm 1a or 1b --- Does that make sense?
Just thought I'd try to think it out --- those could be wrong --- but they're just my ideas... OK?
Although the report from DDW-2007 does specifically answer your question, it does deal with the wild-type variants and the complex issues associated with them. You will either find this fascinating or it will put you to sleep.
GT 1 GT2, etc are genotypes. Within individual genotypes each viron is categorized as a quasispecies. A wildtype can redily replicate any type of quasispecies. Diff drugs are more successful agains some quasi species than others. I remember from a vertex webcast - back when I followed more closely - them explaining that there seemed to be a particular quasispecies that VX wasn't blocking as well as others. The good news was that interferon was very successful against that variat. In mono therapy, patients ended up with a inbalance of virii skewed towards the quasispecies against which vx was less effective.
I guess wildtype can be considered the baseline and the variants are mutations away from it.
I'm confused, as usual. Do you have a wild type virus? Are you going to contact S, but are seeing G? I have the feeling I missed something. The title of your thread and JIm's response made me smile out loud.
Jim: I think any guy that is running around on a scooter after entering the 6th decade could reasonably be considered a wild type. And please don't be so hard on Paris, she's gotten over her wild days and is a role model now:)
This is my layman's understanding - The VX950 molecule was engineered to lock into a pocket on the virus which is unusually shallow. This is the mechanism whereby it disables the virus. When talking about wild-type in relation to the VX treatment I think that wild type virus means the virus with this very shallow pocket. usually the fittest and majority of virus present.
The VX-resistant variants have developed a slightly deeper pocket to which the VX cannot attach. This is how they sneakily escape death by VX and have to be stomped into the ground by SOC.
To the best of my knowledge, a "wild type" virus refers to a viral population that are not selectively bred. A true 100% wild type viral population only exists in a person who is completely treatment naive, or in another words someone who has never taken any antiviral drugs. Wild type means that there can be many slightly differing variants (mutants) with slightly differing features from the "parent" virus (being a 1a, or 1b, 2a, 2b etc etc). There will generally not be a dominant population of a particular subspecies, but a somewhat random mixture of various species still closely related to the original parent virus. There is a great diversity of viral subspecies (or species that have slightly mutated away from the parent), and no selectively bred species within that population.
Once antiviral drugs are taken, the viral population's composition will change in an attempt to survive the effects of the drugs. The viral population will shift away from the random distribution of species generally centered around the parent virus (i.e. the wild types) and towards only the species that are resistant to the anti-viral drug(s) that are being taken. In other words, the anti-viral drug will quickly kill off the viruses that are vulnerable to it - so those viruses will no longer reproduce any more copies of themselves. But amongst that wildtype population there may be just a few floating around that have genetic features that allow it to be resistant to the effects of the antiviral drug - and just a few is all it takes. Since the drug does not kill these viruses off, but it does kill off the ones that are not resistant, you have a "selective breeding" ground going on. Under these circumstances, it won't take long for the dominant viral population to become only drug resistant types. All the non-resistant types are gone and in their place the drug resistant types have filled that void. After this process is complete, you can see a clear distinction between the original viral population (when it was randomly distributed wild types) and the new population, which is comprised only of those capable of resisting the effects of the antiviral drug taken.
You can see this process occur with pretty much any protease inhibitor (like VX950 for instance) when it's given as a monotherapy to a treatment naive patient. Being treatment naive, the patient does not have any selectively bred viral subspecies, just the usual spread of various generally random mutations centered around the parent virus. But amongst that wildtype populace, there will almost certainly be at least just a few viruses that possess randomly mutated characteristics that just by chance will allow them to thwart or resist the effects of the protease inhibitor. So when the protease inhibitor is introduced (as a monotherapy), what you'll see is a sudden and dramatic collapse of the total viral population. Generally within 1 or 2 weeks the viral load is diminished to almost nothing, all of the non-resistant types are wiped out in short order. But then what you'll see is that the measured viral load starts to level off at some low level at or around week 2-3 (this exact timeframe varies depending on the particular drug, virus and patient) and then starts to rebound quickly. Generally within a month after first taking the drug, the viral load has completely rebounded. As described previously, the vast bulk of the wildtype viral population has been wiped out, and is now replaced with only resistant strains that have been selectively bred within the body of the person taking the protease inhibitor as a monotherapy.
Another way of looking at this is to see what happens in nature with animals, which in many ways is analogous of what happens on a bacterial/viral level. For instance, imagine a population of wild dogs running around in a wild environment with no particularly menacing predator or threat to them. The population of dogs is doing well, and are generally thriving in their environment. Now lets say that suddenly one of the dogs encounters a certain deadly form of canine virus that greatly weakens their immune system in a manner that causes death within just a few weeks (causing a type of canine AIDS), and it is easily transmitted from one dog to another via ordinary contact. And lets say that just a few of the dogs (out of hundreds) just by chance have immune systems that are impervious to the effects of the virus. As you can imagine, it won't take long for the vulnerable dogs to die off leaving only the resistant dogs left to fill the void left by them. The resistant dogs will have less competition for the limited resources available and will breed quickly, thereby filling their "new and improved" populace with offspring that have canine AIDS resistant immune systems. Once again selective breeding (or more precisely, selective dying), has given rise to a population that differs starkly from what the original wild type population was.
Lastly, after the shift occurs away from wildtype viral population due to the selective breeding process (as described with the protease inhibitor above), and the impetus for selective breeding is removed (i.e the protease inhibitor is discontinued), the viral population will then begin to drift back into a wild type populace again. In other words, without the pressure of the PI driving selective survival, the dominant viral population (now comprised of PI resistant types) will start to slowly drift away from that dominant strain into generally randomly mutated variants that may or may not necessarily retain the PI drug resistant features that once dominated nearly all of the population. The PI resistant strain isn't particulary better at survival or reproduction than many or most of the other variants, so without the PI around to kill off the non-resistant competition, it has no real advantage any more. Because this is true, over time the viral population will start to take on the features of wildtype again. However, it's important to remember that although the general population may regain a wildtype distribution, amongst those wildtypes there will be a persistent vestige, or long term "memory", of the drug resistant strain that once completely dominated when the PI was introduced. And if that PI were re-introduced (as a monotherapy), even years later, then it could and almost certainly would successfully rise again to become the dominant species as it did in the past.
Oh yeah, one more thing I forgot to mention - the reason scientists and researchers make such a big deal about noting the presence of wildtypes (or lack thereof) is because the presence of wildtypes is suggestive of how effective a particular drug may or may not be. The presence of non-wildtypes is usually suggestive of drug resistant strains that have come about after unsuccessful treatment - which may be suggestive of a viral type that will be unresponsive to another attempt of anti-viral therapy using a drug with the same (or similar) mode of efficacy. The presence of a wildtype population prior to starting treatment is an important parameter to know about when gauging the patient's likely response to whatever antiviral drug(s) are going to be administered. Conversely, the lack of a wildtype population, or the presence of a selectively bred drug resistant population after unsuccessful treatment, is an important parameter to know about when evaluating the long term impact (usually negative) on the patient's ability to treat again using the same (or similar) drugs.
Congrats on the decision to get the second. I got mine from Dr. J. as you know and have NEVER regretted it for a minute (even though I paid $600 CASH to see him). He was MORE than willing to work with and educate my "regular" hepper doc not only in my personal case but also in the latest study info etc.
It showed me just how marvelous these men who are out there digging for information on our disease really truly are. It's not that he just "cared" it is his whole lifes work of which he is passionate as you can imagine.
That gave me so MUCh confidence in my decisions (since they lined up with his) and to me that was so important. Just knowing I was doing the "right" thing helped me to live with it all.
I hope that makes sense but I"m sure you know what I mean.
Meki - I have both geno 1A and 1B (well I should hopefully be able to learn to now say HAD). There was nothing special about it to make it wild type anything...just whomever I got it from probably did drugs with a lot of people and contracted a few types (that is what I assume).
There are a few of us who have it and although treating a combo person SHOULD be exactly the same odds as a single...it does often come back that the person has one very reistant strain versus the other one (ie: Susan400 and her damn geno1A that will not go away while her Geno1B did).
I find out in about three weeks if I am SVR or not. If not - I am going to find out which strain is left cause I"m so nosey I couldn't stand it! But I'd better be SVR anyway :)
Patients with a mutant-type (≥ 4) NS5A–ISDR had a higher rate of SVR (six of nine, 67%) than those with wild-type (five of 22, 23%) (P = 0.038). Stepwise multiple logistic regression analysis of the factors (age, gender, viral load, cirrhosis rate, IFN dosage and amino acid substitutions) revealed that the mutation in NS5A–ISDR (≥ 4 vs< 4) was the only independent variable of treatment outcome.
well, no, I didn't really mean to post the previous comment, but just can't help confusing things further
- "wildtype" is a general biological term meaning those that haven't been mucked with. The mucking can either be drug-based evolutionary pressure, as nicely summarized by mremeet, intentional DNA variations, breeding restrictions, etc. etc. Whenever you're studying an effect, you compare those affected to those unaffected (the wild type). For us it basically means what the virus population looked like before the drugs hit.
- "quasispecies" basically refers to the fact that HCV does a very sloppy job of copying its paltry 9600 base pair genome. By comparison, every time one of our cells divides we have to copy about 2900 million bases - and by golly, we better get it right or cancer and other problems ensue. Because of the sloppy copying, whenever you look at the genomes of an HCV population you're going to see much more variability than among the genomes of a self-respecting species like ours. Hence they got demoted to "quasi".
- re "genotypes" even HCV can't survive if it's RNA blueprint gets too unstable. Some parts of the HCV genome are much better conserved than others - typically those that need to interact with the host systems (us and chimps). Within those conserved stretches you can find some fixed categories - these are the genotypes ( I think we're up to at least 6 for HCV) and the patterns have a definite effect on how virus of that type operates (1s 2s 3s and 4s interact with drugs quite differently). You can slice the classification even finer and get subtypes - but here there is very little evidence of any significant difference (eg 1a vs 1b ). The genotype tests don't actually sequence the RNA (costs too much) so in some cases you get a result that is neither clearly 1a or 1b and you can interpret this as having both but more likely it means you have something with an intermediate sequence. (For those that want the gory details a good site is the LosAlamos hcv sequence database)
The important thing as foreseegood reminded goofy a while back, is that after you go permuting with wild-mutations, the only decent thing to do is to change the sheets.
Meki, you have Genotpye, Subtype and quasi species. Quasi species don’t differ enough to be classified as another geno or subtype. Wild Type basically means many different quasi species.
Variant is a dominant quasi species that is resistant to INF or VX-950 say.
What happens is when an anti-viral applies killing pressure on the virus the main quasi species are killed off. This is what we want to happen. However because the virus breeds so fast a quasi species can develop that is resistant to the anti viral and bingo breakthrough response. This is the variant.
Once the pressure is taken off hopefully the resistant variant returns to the wild type.
This would mean that we could have another go at killing the little buggers.
If the resistant variant remain dominant we would need to use another anti viral to kill it off.
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