Fidelity of target site duplication and sequence preference during XMRV integration

[gu3vara]

Hi Jillbohr

Sorry the excitement of the paper sent me into geek mode

Ok this is my take home message(s)

Our automatic body processes are contolled by the autonomic nervous system.If this becomes dysfunctional then we are left with the neuroendocrine symptoms of ME sensitivity to lights sound ,high resting heartrate POTs poor temperature control and so on.The organic thermostat that controls all these functions is the hypothalamus.When any function such as heart rate strays outside the normal range this is detected by the hypothalamus and brought back into normal ranges by the action of the pituitaty gland and the Adrenal cortex(and medulla).If this control system breaks down our autonomic functions go haywire.

Gerwyn : So I'm understanding that you are pretty confident XMRV could cause CFS based on this science paper? That's awesome news!

I'm just wondering why my girlfriend didn't have CFS after 9 years together and me being sick for 5 years (at least), is it essential to have an already weakened immune system to let it take control of our bodies? (I had some vitiligo since childhood and hashimoto thyroiditis for a long time too and I'm wondering if autoimmune diseases are a consequence or rather the a determinant factor that leave the door open to XMRV).

Would like to know your thoughts on that, thx!

 

[natasa778]

I'm just wondering why my girlfriend didn't have CFS after 9 years together and me being sick for 5 years (at least)

jumping in here...

simplest explanation imo could be that your girlfriend's genetic make-up is such that she is either not suceptible to xmrv infection at all (say through protective polymorphisms in membrane receptors, not allowing xmrv cell entry), or through some immune genes like APOBEC etc that efficiently deal with the infection so it does not take hold (so that she gets infected but xmrv is kept in check straight away).

then more complicated versions of xmrv is there but has randomly inserted into genes that do not cause problems (or 'not YET), in marginal tissue/cells, and it is permanetly latent through good methylation etc etc. or even more complicated versions of her being positive but there would be a need for coninfections, oxidative stress, toxin exposure etc. for xmrv to start causing problems...

 

[gu3vara]

thx Natasa, I sincerely hope that the simplest explanation rules here... I don't want to see her getting sick because of me

 

[alphahusky]

Gerwyn : So I'm understanding that you are pretty confident XMRV could cause CFS based on this science paper? That's awesome news!

I'm just wondering why my girlfriend didn't have CFS after 9 years together and me being sick for 5 years (at least), is it essential to have an already weakened immune system to let it take control of our bodies? (I had some vitiligo since childhood and hashimoto thyroiditis for a long time too and I'm wondering if autoimmune diseases are a consequence or rather the a determinant factor that leave the door open to XMRV).

Would like to know your thoughts on that, thx!

Personally, I think it goes dormant at times. No one I've been with or any family has ever gotten it, though I gave Mono to someone a full year after I had it.

 

[Gerwyn]

jumping in here...

simplest explanation imo could be that your girlfriend's genetic make-up is such that she is either not suceptible to xmrv infection at all (say through protective polymorphisms in membrane receptors, not allowing xmrv cell entry), or through some immune genes like APOBEC etc that efficiently deal with the infection so it does not take hold (so that she gets infected but xmrv is kept in check straight away).

then more complicated versions of xmrv is there but has randomly inserted into genes that do not cause problems (or 'not YET), in marginal tissue/cells, and it is permanetly latent through good methylation etc etc. or even more complicated versions of her being positive but there would be a need for coninfections, oxidative stress, toxin exposure etc. for xmrv to start causing problems...

polymorphism in XPR-1 receptor could be a factor.XMRV could cause illnesses not recognisable as ME high blood pressure tacycardia osteoporosis anciety etc gastric problems asthma the list is pretty long

 

[gu3vara]

Wow, XMRV discovery could turn out to be the greatest things since bread came sliced...! Imagine if it was involved in some serious autoimmune disease like lupus or MS too.

It now seems we are closer to the Nobel prize than the flop...thank god for that

 

[JillBohr]

Thank you Gerwyn. Sorry it to long to thank you but when I read your response.....

The excitement set off my autonomic nervous system. Which then became dysfunctional which left me with the neuroendocrine symptoms of ME sensitivity to lights, sound, high resting heartrate POTs poor temperature control and so on. As you know, the organic thermostat that controls all these functions is the hypothalamus and when any function such as heart rate strays outside the normal range this is detected by the hypothalamus and brought back into normal ranges by the action of the pituitaty gland and the Adrenal cortex (and medulla). So the control system broke down my autonomic functions and then went haywire.

Oh..... I am so thankful to have you geeks here.

 

[Robyn]

Has this been posted anywhere yet? Let me know and I'll delete if needed.

New pubmed abstract:

http://www.prohealth.com/fibromyalgia/blog/boardDetail.cfm?id=1389662

 

[jewel]

Amazing explanations, Gerwyn and Natasa. Thanks, J.

 

[citybug]

The science is excellent.It is what I have been hoping for. XMRV was originally found inserted within CREB genes.CREB genes are regulatory genes which affect systems all over the body. I have the hypothesis that XMRV does irs dirty work by causing the creb gene to malfunction.Untill this paper there was no actual evidence that XMRV could affect the CREB gene in this way.Insertional mutagenesis is such a mechanism.Xmrv can act as a duplication mutation or a deletion.Either way the proteins formed from CREB would be abnormal and affect their regulatory function.with this paper at last we have a mechanism how such a "simple" virus could cause multi systemic disease.We have an explanatory model to club Drs with.

When scientists read this study are they going to get the CREB and NFAT effects immediately or do you need to understand ME/CFS?

 

[citybug]

simplest explanation imo could be that your girlfriend's genetic make-up is such that she is either not suceptible to xmrv infection at all (say through protective polymorphisms in membrane receptors, not allowing xmrv cell entry), or through some immune genes like APOBEC etc that efficiently deal with the infection so it does not take hold (so that she gets infected but xmrv is kept in check straight away).

Are there any treatment possibilities that address the receptors?

Is this right-Those are the human cell receptors and cortisol, progesterone, testosterone and cytokines? for inflammation attach to the xmrv receptors?

 

[helsbells]

I too just want to thank the geniusus (geniai??) who take the time and trouble to break this down for brain addled, long time affecteds' like myself. It is beyond kind to take the trouble of sharing what you understand. I am struggling terrifically with MCS at the moment ( an unavoidable house move radiator paint, dust, perfume smell etc etc etc etc ) and actually coming and reading this stuff really lifts me from much darker thoughts. Thank you so much

 

[natasa778]

Are there any treatment possibilities that address the receptors?

No, not for the XPR1 receptors, as far as I'm aware. That one is the primary xmrv entry receptor. There may be others it uses in additon to xpr1 (currently being researched) for which there could be receptor blockers already out there.

Sorry I don't understand the rest of your question.

 

[subtr4ct]

Has this been posted anywhere yet? Let me know and I'll delete if needed.

New pubmed abstract:

http://www.prohealth.com/fibromyalgia/blog/boardDetail.cfm?id=1389662

It seems to be new. I also saw it go by on the Google Alert yesterday. Seems to be just a review/survey piece. Interesting that it appears in an allergy focussed journal. May have some interesting speculation regarding the subtle immune effects seen in CFS that could be caused by XMRV. No time to read it at the moment... Seems like it probably deserves it's own thread, even if it's nothing earth-shattering.

 

[hvs]

simplest explanation imo could be that your girlfriend's genetic make-up is such that she is either not suceptible to xmrv infection at all (say through protective polymorphisms in membrane receptors, not allowing xmrv cell entry), or through some immune genes like APOBEC etc that efficiently deal with the infection so it does not take hold (so that she gets infected but xmrv is kept in check straight away)...

This might be right, or it might not be genetics but rather that it's
1. actually quite hard to pass along, but given enough time and enough hanky-panky one probably will
2. one's partner might have it but it's not manifesting as something that looks like XAND/"cfs" [I believe that Gerwyn stated something like this]

 

[Gerwyn]

No, not for the XPR1 receptors, as far as I'm aware. That one is the primary xmrv entry receptor. There may be others it uses in additon to xpr1 (currently being researched) for which there could be receptor blockers already out there.

Sorry I don't understand the rest of your question.

i think this is very tentative that they may be greater in number and or slightly different in structure in men and women

 

[V99]

This was posted on co cure http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1004E&L=co-cure&P=R307

Have a look at the part in red where they discuss prostate cancer. Is this another study they are talking about? or the one already mentioned?

Removed this bit as I believe it has not been published yet.
--------------------------------------------

P53

'Prevalence of XMRV in prostate cancer and chronic fatigue syndrome
patients in Germany'
O. Hohn1, K. Strohschein2, H. Krause3, R. Kurth1, C. Scheibenbogen2, N. Bannert1
1 Robert Koch-Institute, ZBS4, Berlin, Germany
2 Charit - Universittsmedizin Berlin, Institute for Medical
Immunology, Berlin, Germany
3 Charit - Universittsmedizin Berlin, Urology, Berlin, Germany

Background: A novel gammaretrovirus named xenotropic murine leukemia
virus-related virus (XMRV) has been recently identified and found to
have a prevalence of 40% in prostate tumor samples from US American
patients carrying a homozygous R462Q mutation in the RNaseL gene. More
recently XMRV has also been found in up to 67% of US American patients
suffering from chronic fatigue syndrome (CFS) without any correlation
to the RNaseL genotype. The aim of our study is therefore the
determination of the XMRV prevalence in prostate cancer cases and in
CFS patients in Germany.

Methods: Real-time PCR was used for RNaseL genotyping of prostate
cancer samples. Highly sensitive nested PCR and RT-PCR approaches were
applied for the detection of XMRV gag sequences. Using recombinant
Gag- and Env-proteins an ELISA was developed for the detection of
anti-XMRV antibodies in human sera samples.

Results: 589 prostate tumor samples were genotyped by real-time PCR
with regard to the RNaseL mutation. In agreement with earlier data,
12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV
specific sequences were detected at neither the DNA nor the RNA level
and none of the 146 sera analyzed from prostate cancer patients
contained XMRV-specific antibodies. The outcome of the ongoing CFS
study will be presented at the conference.

Conclusion: Our results indicate a much lower prevalence (or even
complete absence) of XMRV in prostate tumor samples in Germany. One
possible reason for this could be a relatively recent acquisition of
the virus from a murine host and a geographically restricted incidence
of XMRV infections.

 

[Gerwyn]

This was posted on co cure http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1004E&L=co-cure&P=R307

Have a look at the part in red where they discuss prostate cancer. Is this another study they are talking about? or the one already mentioned?

hohn produced the other negative study .In fact This appears to be the same one!

589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies.

Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections.
Background

compared with

Results: 589 prostate tumor samples were genotyped by real-time PCR
with regard to the RNaseL mutation. In agreement with earlier data,
12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV
specific sequences were detected at neither the DNA nor the RNA level
and none of the 146 sera analyzed from prostate cancer patients
contained XMRV-specific antibodies. The outcome of the ongoing CFS
study will be presented at the conference.

Conclusion: Our results indicate a much lower prevalence (or even
complete absence) of XMRV in prostate tumor samples in Germany. One
possible reason for this could be a relatively recent acquisition of
the virus from a murine host and a geographically restricted incidence
of XMRV infections.

------------------------------------- THIS IS NOT A NEW STUDY BUT THEY ARE BOLTING ON CFS TO A STUDY THAT WAS NOT DESIGNED TO INVESTIGATE ME AT ALL!

ANYONE KNOW WHEN THIS IS GOING TO BE PRESENTED ESPECIALLY IN RELATION TO DR JUDY,s WORK

 

[V99]

Sorry Gerwyn I meant the CFS study they mention. Are they saying more info is coming on CFS XMRV?

 

[Gerwyn]

Sorry Gerwyn I meant the CFS study they mention. Are they saying more info is coming on CFS XMRV?

the prostate cancer part of the"study" is identical to their study already published.They have merely added the cfs bit retrospectively