New study - prospects for the treatment of retroviral diseases

[thefreeprisoner]

@Eric, Please please PM the text to _Kim_ so she can add it to our private library here. You're an absolute gem and managed to explain this so well so that even a brain-fogged arts graduate can understand it

Gerwyn and Natasa... hats off to you to for making this all possible.

Rachel xx

 

[Gerwyn]

OK, I've read much of it. This will be a crude once-over synopsis.

Basically, these people discovered that certain retroviruses including XMRV encode a piece of a molecule with a very potent immunosuppressive function. They made mutant viruses which lack this function, and those viruses basically could not infect mice.

To give a little more detail for those with some background, it seems the Env (envelope) protein of a group of retroviruses including XMRV is not just an envelope protein. It is within the Env that this group discovered this potent immunosuppressive domain which.

The weak mutant virus without the immunosupressive domain fails to infect normal mice. It does better when the mouse's NK and CD8 cells are hampered artificially. Therefore, the new immunosuppressive domain somehow puts a damper on these immune cell types doing their thing. Which is of course to kill varmints like retroviruses et al.

The weak mutant virus induced a much stronger immune response. Why Mister, lymphocytes were spewing much more IFNg and other fine molecules that would, when produced in sufficient quantities, kill stuff and resolve an infection.

So, if a drug can inhibit thise immunosuppressive molecule domain robustly, that alone might plausibly bring the immune system around, to the extent that it would suppress XMRV to non-pathogenic levels and you would feel fine. What's not clear, apparently, is what that little domain is and does. Therefore, it doesn't necessarily have to be druggable, but my half-informed guess is that the chances are probably pretty fair. Some types of interactions that *might* be occurring here, namely protein-protein interactions, can be relatively difficult to inhibit well with drugs -- but that doesn't necessarily mean it can't be done. Especially when there is a huge amount of potential revenue to be made, which means we might see very large and very flush research projects in several firms (almost all drug discovery is done by the private sector, which has a lot more dough than government entities like NIH).

I wonder if it would be possible to transpose retroviral gene silencing suppressor analogues using xmrv intergegrase as the base sequence

 

[omerbasket]

I didn't understand exactly what you mean, Gerwyn (becuase I'm not a scientist), but I think that perhaps my following questions would be similar to your message. My questions for the people who knows science here are:
1) Do you think it might be possible that if you give someone who is already XMRV positive a shot which contains XMRV viruses (perhaps weakened viruses) but without the potent immunosuppressive domain which this study found in the virus envelope - would be able to teach this someone's body how to kill XMRV and there for might teach his body how to kill the regular XMRV, which has already been in his body and have this potent immunosuppressive domain?
2) Do you think that giving someone a shot of this potent immunosuppressive domain alone (without the rest of the virus), perhaps in some weakened version might teach the body how to deal with it, and therefore teach the body how to kill the XMRV that is also in the body?
3) Do you think that giving someone a shot of a weakned XMRV, containing a weakened version of this potent immunosuppressive domain, might teach the body how to kill the XMRV that is already in the body?
4) Do you think that this discovery might open a promising door for vaccines for those who don't have this retroviruses in their body?

I would be happy if even in case in which you write your answer in scientific words, you would try to give a bottom line in a language that we would all understand (if it's possible).

Thanks!

 

[Gerwyn]

I didn't understand exactly what you mean, Gerwyn (becuase I'm not a scientist), but I think that perhaps my following questions would be similar to your message. My questions for the people who knows science here are:
1) Do you think it might be possible that if you give someone who is already XMRV positive a shot which contains XMRV viruses (perhaps weakened viruses) but without the potent immunosuppressive domain which this study found in the virus envelope - would be able to teach this someone's body how to kill XMRV and there for might teach his body how to kill the regular XMRV, which has already been in his body and have this potent immunosuppressive domain?
2) Do you think that giving someone a shot of this potent immunosuppressive domain alone (without the rest of the virus), perhaps in some weakened version might teach the body how to deal with it, and therefore teach the body how to kill the XMRV that is also in the body?
3) Do you think that giving someone a shot of a weakned XMRV, containing a weakened version of this potent immunosuppressive domain, might teach the body how to kill the XMRV that is already in the body?
4) Do you think that this discovery might open a promising door for vaccines for those who don't have this retroviruses in their body?

I would be happy if even in case in which you write your answer in scientific words, you would try to give a bottom line in a language that we would all understand (if it's possible).

Thanks!

There are certain vaccines that only contain bits of the virus sufficient for the bodies immune system to react to at a subclinical level.the immune system then retains a memory of this bit of the virus so when the whole thing infects the immune system"is lying in wait" for it.So if the sequence in the env protein is big enough to be recognised as foreign by the immune system you could theoretically construct a vaccine

answer to 2 and 4 yes in theory

I and 2 no I dont think so The virus titres(no of virus particles) are low so most of the virus appears to be hiding in the host DNA where it seems to cause most of the damage . It seems to be doing something to the neighbouring bits of DNA which in turn dont do what they should. Somewhere in our history we developed a special defence against retroviruses in particular called gene silencing . The dna sequences either side of the integrated viruses "switch off" to stop the viruses hijacking our DNA to replicate itself.Retroviruses in turn have adapted to produce gene silencing suppressor sequencesuch as AIDS.XMRV may actually have adapted to make use of this natural gene silencing leading to an underexpression of genes needed for the immune system to work properly.My suggestion was to introduce an artificial analogue to stop this gene silencing and get the immune system working properly again----This is theoretical---a way of explaining why xmrv can damage the immune system without coding for any destructive proteins

 

[Eric Johnson from I&I]

1. plausible 2. naw 3. plausible 4. plausible

 

[Gerwyn]

1. plausible 2. naw 3. plausible 4. plausible

4 the most likely subunit vaccines are quite successful 2 possible competitor activity might inhibit immunosuppression ability of Wt base sequence still think 1 and 3 no as most virus latent if studies are correct!

 

[omerbasket]

Thanks Gerwyn and Eric, once again!

 

[Rrrr]

bumping this thread, because it is so freaking good.

rrrr