IDENTIFICATION OF A NOVEL RETROVIRUS IN PATIENTS WITH BPH

[Firestormm]

Perhaps they should add a further description to this category on the forum? 'Other retroviral studies' or 'New retroviruses?' and separate out XMRV seeing as that now seems to have been, well, you know history, until/if someone publishes a new paper linking it to human disease. I mean some of these papers are hardly 'replication' efforts are they?

 

[Dan_USAAZ]

Perhaps they should add a further description to this category on the forum? 'Other retroviral studies' or 'New retroviruses?' and separate out XMRV seeing as that now seems to have been, well, you know history, until/if someone publishes a new paper linking it to human disease. I mean some of these papers are hardly 'replication' efforts are they?

For those members that are interested in continued viral research, I believe the conversation shifted from XMRV to a much broader definition a long time ago. It appears to be the people opposed to viral research and its possible association with ME that focus on just XMRV (VP62) and keep sending the debate back to just that narrow definition.

 

[Firestormm]

Whatever. My point simply was that this category on this forum only portends to XMRV. It is titled 'XMRV Research and Replication Studies'. The previous comment was suggesting that folk might have missed some of the new studies, and my suggestion was an attempt to draw greater attention to them i.e. by adding a new category for folk who wish to continue discussing 'retroviruses' even if they are unconnected (at this time) with ME.

 

[natasa778]

Whatever. My point simply was that this category on this forum only portends to XMRV. It is titled 'XMRV Research and Replication Studies'. The previous comment was suggesting that folk might have missed some of the new studies, and my suggestion was an attempt to draw greater attention to them i.e. by adding a new category for folk who wish to continue discussing 'retroviruses' even if they are unconnected (at this time) with ME.

the fat lady has not sung yet whatever you like to believe

http://forums.phoenixrising.me/inde...t-of-12-cfs-patients-positive-for-mulv.18706/

 

[Mark]

This perhaps doesn't fit precisely under the XMRV heading but it seems to me a little premature at this stage to create a new forum for MLVs and retroviruses in general. We wouldn't want to create a new section unless (a) the separation between the forums is very clearly and unambiguously defined, and (b) there is enough content to justify a new forum. I'm not sure that's the case at the moment, though it may perhaps become necessary. And it's generally the case that forums contain some content that is tangentially related to the subject, that's OK if there's no better place for it and the content is broadly relevant to the forum subject.

In this case, the BPH paper states that "The BPH viruses disclosed herein are related to previously identified gammaretroviruses such as murine leukemia virus and xenotropic murine leukemia virus-related virus (XMRV), but are distinct from these viruses based on nucleic acid and amino acid sequences". So it seems reasonable to mention, within the XMRV sections, research into related gammaretroviruses; we don't want a different forum for each different gammaretrovirus...

I think it's also worth pointing out how this name game has worked out. The original (VP62) was named Xenotropic Murine Leukaemia Virus Related Virus. Now: any other MLV-rs and other similar gammaretroviruses that are posited, like this one, if they are Xenotropic (to mice), are Xenotropic viruses related to MLVs. So they may not be "the" XMRV, as it has been tightly defined, but in that sense they are "XMRVs" if they fit the same definition that caused that name - that is, they are xenotropic viruses related to MLVs - and quite likely many viruses will fit that definition. After all, how likely is it that the recently-discovered accidental lab-creation of XMRV in a common lab procedure is the only MLV-related gammaretrovirus that has ever been so created?

Properly, following the examples of HIV and HTLV, one might normally expect viruses such as the one now being associated with BPH to eventually be called XMRV-1, XMRV-2, etc. Clearly that isn't going to happen in this case, because "XMRV" as such has effectively been tightly defined out of existence/relevance, but at this stage that does seem more like a political use of definitions and nomenclature than a logical one; perhaps there will come a point when future viruses like this one need a name, and it may become difficult to figure out what to call them if you're not allowed to call them XMRVs...or indeed HGRVs...

 

[Bob]

...we don't want a different forum for each different gammaretrovirus...

Now there's a good idea... The mods could create a new sub-forum for each new variant that is registered with genbank... Think how well organised our forum would be! (Only joking, Mark, obviously )


On a slightly more serious note, I do agree that a new sub-forum isn't needed, in my opinion... We all post any XMRV-related research in the XMRV forum. The XMRV sub-forum could easily be relabelled as "XMRV-related research and replication studies", but it doesn't need to be, as that's how it's used anyway.

 

[ukxmrv]

I agree that these are not replication attempts but they are all connected to the work done at the WPI and the original Science paper.

Dr Mikovits was talking about MLV's and not XMRV very early on. Most noticably at the time of the Alter / Lo paper. She was talking about a possible family of MLV's. It's this thread that lagged behind her.

Maybe we should have changed the title of this thread back then as things developed away from what was called XMRV to MLV's?

Personally I'd like to keep it all together as a discussion of theMLV retrovirus connection to CFS and ME unless a new paper is published on an entirely different retroviral family implicated in these diseases and it looks as if the discussion of MLV's is a seperate issue.

 

[Firestormm]

the fat lady has not sung yet whatever you like to believe

http://forums.phoenixrising.me/inde...t-of-12-cfs-patients-positive-for-mulv.18706/

Rather harsh calling Lipkin 'fat' (or a lady for that matter) don't you think

 

[natasa778]

Lipkin won˙t be the final word, whatever the findings. In another time and place this desparate need of some people to look the other way would make a nice case study ...

 

[Firestormm]

He he he he he... Rather harsh inferring that I am looking the other way, when I seem to spend so much time reading these threads and the research, if not always commenting very positively....

 

[currer]

I think Nastasa was probably refering to the retrovirology community Firestormm.

If MLVs have already been passed into the population / already exist in the population and are causing disease there will be commercial consequences.
The therapeutic patenting of modified retroviruses for gene therapy will need to be looked at again, because although the vectors are modified so that they only undergo one replication cycle ( and hence cannot spread) they could recombine with MLVs if they are already present.

These technologies are only conceivable on a theoretical basis of control over the unknown and unpredictable - so there is a tendency to ignore the unconformable.

It is understandable that this would be unwelcome news.

 

[Firestormm]

You know I really think the 'cat is out the bag' now, well and truly, about the XMRV 'family' of retroviruses. The 'Lipkin Study' which might have been finished a long time ago after all, is being referred to as 'definitive' by Mikovits and Alter because it is the only remaining state funded enquiry attempting to replicate the results alleged and kicked-off by the Lombardi paper and then added to by Lo. We are seeing more and more general papers being published in this area all the time. I really don't think it will 'go away' but I do think it will require a very carefully thought through paper attempting to link any one of these viruses to humans let alone ME and any specific disease. Lombardi and all that has happened since has really raised awareness about the presence of some of these viruses and of their nature. General research into murine viruses won't suddenly stop.

Edit: I forgot they're also looked for the 'MRV's that were 'found' in Lo et al too of course.

 

[Bob]

We are seeing more and more general papers being published in this area all the time. I really don't think it will 'go away' but I do think it will require a very carefully thought through paper attempting to link any one of these viruses to humans let alone ME and any specific disease. Lombardi and all that has happened since has really raised awareness about the presence of some of these viruses and of their nature. General research into murine viruses won't suddenly stop.

Yes, I agree with you on all of these points Firestormm.
MLVs won't go away, and research will continue, but it requires some very sophisticated research to find out exactly where all of these sequences are coming from, and to convincingly link the field to human disease, if there is a link.
Without any doubt, I'm certain that retrovirology will move towards finding out where all the MLV-like sequences originate from, over the next few years.

 

[currer]

Even if they are in people and benign they will not be able to go ahead with gene vectors based on MLVs.

I dont know how much has been invested into this area of biotechnology - but it will be a lot.

A Natural Human Retrovirus Efficiently Complements Vectors Based on Murine Leukemia Virus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519784/
The fact that a popular class of retroviral vector could readily become infectious in the presence of natural human virus has to be seriously considered whenever these constructs are being used, especially in a clinical setting. The most obvious concern is the possibility that a vector could accidentally encounter XMRV and would spread in human populations. In the case of gene therapy, the therapeutic construct might spread from the intended tissue target throughout the organism or even to additional individuals. An even more deleterious, albeit less probable, event might be an accidental escape of an experimental vector that harbors an oncogenic “cargo”. Modern MLV-based vectors have undergone extensive engineering to improve their performance in specialized tasks [1]. For example, mutations in the long terminal repeats have been used to improve expression, especially in embryonic cells[17]. An escape of such constructs would open a possibility for recombination with natural viruses, potentially increasing pathogenicity of the latter.

While the virion may infect naïve cells, resulting in integration of the provirus in the DNA of the new host, the genes encoding the packaging proteins normally will not be transferred. Consequently, no further replication of the vector occurs and the virus will not spread beyond the progeny of the originally infected cell. This condition is heavily relied upon when the use of such vectors is considered. The situation would radically change if the viral proteins are expressed in the transduced cell, as might happen, for example, when the same cells are inhabited by a replication-competent MLV variant. This is a serious concern for the use of MLV in murine cells, where closely related retroviruses are sometimes found [2].

 

[natasa778]

Even if they are in people and benign they will not be able to go ahead with gene vectors based on MLVs.

I dont know how much has been invested into this area of biotechnology - but it will be a lot.

A Natural Human Retrovirus Efficiently Complements Vectors Based on Murine Leukemia Virus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519784/

Very interesting! Probably merits a thread of its own?

 

[currer]

Actually Nastasa this paper was discussed at the time it came out. I dont know if it has a thread of its own though.

It is one of Silvermans early papers at the time of the initial XMRV discovery. It has a very interesting discussion section explaining exactly how these new viruses would be a problem for gene vector technology. The financial consequences would be immense if (wild) XMRVs were accepted. And the wild XMRV - type virus would not even need to be a pathogen, just present.

So I think this a very interesting paper for lots of reasons and one that should not be forgotten.
I repost it as it is easy for us to forget significant research from a couple of years ago and also because there are new members of PR who will never have seen it before, and we need to bear them in mind in our discussions here.

 

[tonydewitt]

My understanding is that several Leukemia Viruses exist (Simian, Human, Bovine, Murine, Feline, etc). The human version jumped from apes to humans 100,000 years ago, and perhaps the mouse version has jumped to humans as well (more recently, as is the case is HIV). My belief is that all of these Leukemia Viruses are very closely related in terms of the disorders they cause to humans, so in that sense, giving them new names is confusing, and viewing them as separate entities is a waste of time also. I've been sick for a year, and have symptoms of HTLV, but can't test positive for it through several antibody tests (along with a PCR test). No doctor is going to tell me what I have, but if any of you asked me what we all have, my answer to you would be that we have a Leukemia Virus. Which one you might ask? Why does it matter would be my reply. What matters to me (and to all of us) is that we find some treatment that brings us relief from our suffering. Since the virus survives by taking advantage of inflammation factors, shutting down inflammation is a viable antiviral approach. Other approaches are generic antiviral therapy (e.g. Lysine), along with epigenetic modifiers (Azacytidine), and demethylating agents (green tea tablets).

Here's the list of treatment options that I've come up with so far:

(1) Anti-inflammation (over the counter supplements): Curcumin and wedelolactone tablets block kinase inflammation signals (JAK, IKK, CDK, and Nf-Kb) that Leukemia Viruses use to survive.
(2) Anti-inflammation (pharmaceutical drugs effective against LV): Tofacitinib shown effective against HTLV by inhibiting Janus kinase (JAK). Approved by the FDA for 11-21-2012.
(3) Anti-inflammation (pharmaceutical drugs effective against LV): BMS-345541 and Purvalanol-A shown effective against HTLV by inhitibiting kinases IKK and CDK respectively.
(4) Demethylating agents: Fucoidan and green tea tablets limit viral reproduction via demethlyation.
(5) Anti-viral (over the counter supplements): Lysine.
(6) Epigenetic modifiers: Azacytidine (Vidaza) successfully treated a 58 year old HTLV patient in Greece; not only does Azacytidine 'correct' aberrant cell function, but also it serves as a demethylating agent, limiting viral reproduction.
(7) Hyperthermia: Suggested as a treatment for HTLV in a paper by Hatanaka, and provided by the Siberian Research Institute of Hyperthermia (bringing the body temperature to 111 degrees F).
(8) Anti-viral (compounds effective against any virus): DRACO, a broad spectrum antiviral created by Dr. Todd Rider of MIT, has been shown effective against 15 different viruses. As time and funding permit, Dr. Rider and his team will continue to test DRACO against ALL known viruses, with the eventual goal of proving that DRACO works against ANY virus, including Leukemia Viruses.

Two people mentioned on the HTLV help Face Book page work with floors (one is a floor installer, the other is a floor washer), both are practically wheel chair bound by the virus, and both are married with children. Fortunately, their spouses and children are not sick. How do two people in monogamous marriages (and non IV users) with children become infected? They both have floors in common, and floors are where mice are found, so therefore I believe that they were infected through their jobs working with floors. This brings my point full circle that whatever Leukemia Virus you might have, its spread is ubiquitous enough that we're seeing people (who aren't in a high risk group like these two people) getting sick, so sick that they cannot walk. Add to that the 58 year old HTLV patient in Greece (married, with a HTLV negative wife) who became deathly ill and was saved by 8 months of Azacytidine treatments. Again, leukemia viruses are becoming so prevalent that they can no longer be attributed to classic high risk groups (gays, IV drug users, prostitutes, etc). Since the medical industry refuses to help us, we need to help ourselves - I would recommend that anyone who can get access to Tofacitinib when it becomes available (supposedly November 21, 2012) do so. If this drug alleviates your suffering, you will have reached the first plateau.

Best wishes.

 

[ukxmrv]

Thanks Tony! That's fasinating stuff.

 

[anciendaze]

Perhaps those here can assist me in checking a recent letter to Nature on Resurrection of endogenous retroviruses in antibody-deficient mice. I've read over this material a couple of times, and still find no direct references to the possibility of contamination of those mouse colonies by exogenous retroviruses. Are there any indirect references I am missing? With the exception of colonies kept in completely germ-free environments there appears to be little or no concern that those exhibiting resurrected ERVs might have had retroviral contamination, of which we have heard so much elsewhere, to start the process.

Two points I mention w.r.t. this striking phenomenon: 1) all the "resurrected" retroviral strains they found showed a series of recombination events with known ERVs; 2) the role of microbiota in inducing clonal expansion of immune cells is addressed indirectly via antibody response without concern that this expansion may in fact be the key to bringing copy numbers of retroviruses known to infect these cells up to the level where they can be detected.

My problem is that a series of recombination events resulting in a replication-competent chimera of different ERVs doesn't proceed unless each stage in the sequence results in a replication-competent retrovirus. It is a lot easier to explain the process if the starting point is a fully replication-competent retrovirus which is simply outnumbered by those ERVs whose transcription is activated by the same conditions. If you aren't able to examine the early recombinants you are unlikely to identify the exogenous trigger at a much later date.

Implications for human health should be obvious, considering the much larger numbers of humans currently surviving with immune impairment due to one or two retroviruses. I'm not even sure we know how many are actually infected with HTLV-1.

A surprising number of chronic or slowly progressive human diseases do show a pattern of appearance or aggravation following an episode of immune impairment. Some research has found evidence of reactivated HERVs, though all this is contentious. This could be behind the last 40 years of failure to solve the question of etiology of those diseases.

 

[GcMAF Australia]

The human genome is composed of viral DNA: Viral homologues of the protein products cause Alzheimer's disease and others via autoimmune mechanisms.
Christopher J. Carter1


The human genome is composed of millions of fragmented contiguous viral DNA sequences, dating from the dawn of evolution and reflecting retroviral insertions over millions of years of coexistence. Herpes and other viral insertion points correspond to the locations of over 120 Alzheimer's disease susceptibility genes and to linkage hotspots. The greater the number of pathogen matches, the more important the gene. These DNA sequences are translated into short contiguous 5-12 amino acid stretches (vatches), identical in viruses and man, and in other pathogens implicated in Alzheimer's disease (Borrelia, Chlamydia, Helicobacter, C. Neoformans , P. Gingivalis). C. Neoformans, which has been associated with a rare but curable form of dementia, expresses the most number of hits to Alzheimer's disease proteins. Vatches are often immunogenic and antibodies to viral proteins may knock down their human counterparts or activate immune responses killing the cells containing their human homologues. This is supported by the presence of the complement membrane attack complex in Alzheimer's disease neurones and by the ability of tau antigens (homologous to pathogen proteins) to promote the formation of neurofibrillary tangles and Alzheimer's disease pathology in mice. Vatches may act as dummy ligands or decoy receptors and interfere with the interactome of their human counterparts. Alzheimer's disease is thus a "pathogenetic" disorder caused by pathogens but dependent on the genes that create these matching sequences. This scenario is relevant to many other, and perhaps most human disorders, given the massive genomic extent of viral coverage. The vatches in the human proteome, dictated by polymorphisms and mutations, may predict, from birth, the spectrum of pathogens that match our proteins and which pathogenetic disease we are likely to develop. These may all be preventable by vaccination, pathogen detection and elimination and curable by immunosuppressant approaches, perhaps with a unique, safe, and effective immunosuppressant panacea.