• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

IDENTIFICATION OF A NOVEL RETROVIRUS IN PATIENTS WITH BPH

natasa778

Senior Member
Messages
1,774
Not sure if this has already been posted (or has its own thread?)

IDENTIFICATION OF A NOVEL RETROVIRUS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA
Inventors:
O'keefe, Denise S. (Wexford, PA, US)
Application Number:
13/282888
Publication Date:
05/03/2012
Filing Date:
10/27/2011
http://www.freepatentsonline.com/y2012/0107338.html

... Disclosed herein are novel retroviruses associated with BPH and viral nucleic acids and polypeptides encoded by such nucleic acids. Also disclosed are methods of detecting presence of BPH virus in a sample from a subject and agents that can produce an immune response to a BPH virus that can be used for treatment and/or protection from a BPH virus infection. 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. Therefore, the methods disclosed herein include methods of specifically detecting BPH virus (such as a BPH virus polynucleotide or polypeptide) in a sample from a subject, for example discriminating the presence of BPH virus in a sample as opposed to XMRV. In some examples, the disclosed methods include detecting the presence of a BPH virus and the absence of XMRV in a sample from a subject.

... BPH virus: A retrovirus identified in prostate samples from subjects with BPH. The BPH virus is distinct (for example at the nucleic acid or amino acid level) from XMRV. In particular examples, a BPH virus includes one or more nucleic acids having at least 75% identity (such as at least 80%, 85%, 90%, 95%, or more identity) with a nucleic acid sequence set forth as any one of SEQ ID NOS: 1-38, or the reverse complement thereof, wherein the nucleic acid sequence is not an XMRV nucleic acid sequence. In other examples, a BPH virus includes one or more polypeptides having at least 75% identity (such as at least 80%, 85%, 90%, 95%, or more identity) with an amino acid sequence set forth as any one of SEQ ID NOS: 39-58...

... It is disclosed herein that several viral polynucleotides or polypeptides encoded by such polynucleotides can be used to diagnose an individual with BPH or at risk for developing BPH. Such polynucleotides or polypeptides encoded by such polynucleotides (or immunogenic fragments thereof) can also be used to induce an immune response to BPH virus to inhibit or treat BPH. The BPH virus polynucleotides and polypeptides disclosed herein are distinct from previously identified XMRV both at the molecular level and clinically (for example XMRV has been identified in prostate cancer samples, but has not been identified in BPH samples). In some examples, a BPH virus polynucleotide or polypeptide is not an XMRV polynucleotide or polypeptide if the nucleic acid or amino acid sequence is not identical to an XMRV nucleic acid or amino acid sequence (such as the XMRV sequences disclosed in PCT Publication No. WO 06/110589)...
 

natasa778

Senior Member
Messages
1,774
more interesting bits:

EXAMPLES

Example 1

BPH Virus Primers

Primers for virus amplification were designed based on homology between XMRV and related viruses (e.g., murine leukemia virus), making the assumption that these similarities would be the most conserved regions of this family of retroviruses. The primers are shown in Table 1.

...
Fifteen of twenty BPH samples produced an amplified product with the gag primers shown in Table 1, while only three of twenty donor samples were amplified by these primers (FIG. 1). An immortalized, presumably non-diseased prostate stromal cell line (WPMY-1), also produced an amplified product with the gag primers, however the LNCaP prostate cancer cell line and the immortalized prostate epithelial cell line RWPE-1 did not produce an amplified product (FIG. 1). A genomic PCR was performed on all samples to determine the integrity of the DNA. For the ARE region, 4 BPH samples were tested and all were positive, as were the PC3 and WPMY cell lines; however, the LNCaP cell line was negative. For the variable envelope region HB068 and WPMY and PC3 were positive, while LNCaP was negative.

The gag sequences obtained from the BPH and donor samples were not identical to any sequences from viruses know to infect humans. An alignment of the glyco-gag sequences is shown in FIG. 2 and a dendrogram showing the relation of these sequences to XMRV is shown in FIG. 3. Based on the gag sequences, two genetically different BPH viruses have been identified; these have been designated BV1 and BV2. The BV1 sequences include an open reading frame that utilizes an alternative start codon, which produces a glyco-gag protein. This protein is predicted to be inserted in the cell membrane and does not become a structural part of the virus. The cell surface location of this protein makes it a target for vaccine design.

The sequence identity between the amplified gag, envelope, and variable region sequences and XMRV is shown in Table 3. Sequences obtained from the gag region from 17 BPH samples, 2 normal prostate tissues from organ donors, and the BPH and WPMY cell lines were compared. Slight variations were identified between the sequences even within the same patient's tissue, suggesting that the virus may be actively replicating and acquiring mutations.
 

natasa778

Senior Member
Messages
1,774
Example 5

Anti-Viral Response in BPH Samples

This example describes the presence of an anti-viral response in samples from subjects with symptomatic BPH.
Inflammation is commonly observed in BPH. In support of this and our data demonstrating the presence of virus in symptomatic BPH/TURP samples, an anti-viral immune response was observed in BPH samples. Expression of genes involved in the anti-viral immune response was measured in BPH tissues from men undergoing transurethral resection of the prostate (TURP) to alleviate symptoms, asymptomatic BPH (histologic BPH obtained from men undergoing prostatectomy for prostate cancer with AUA symptom scores less than 12), no BPH (normal transitional zone from cancer patients), and histologically normal prostate tissue from organ donors.
Complement factor I (CFI) was significantly upregulated in the tissue samples from symptomatic patients when compared to the other three tissue types (p<0.012). CFI inactivates C3b and C4b, two key players in activation of the complement pathway. Additionally, 2′-5′-oligoadenylate synthase (OAS2) was significantly upregulated in symptomatic BPH compared to asymptomatic BPH (p=0.004). OAS proteins recognize the double-stranded RNA of viruses. Without being bound by theory, it is believed that in the presence of virus in symptomatic BPH, CFI expression is deactivating the complement pathway, allowing for viruses to infect cells of the prostate. OAS2 is then likely being induced due to the presence of virus.

Example 6

Detection of BPH Virus in a Sample

...In some examples, detection of a BPH virus nucleic acid, polypeptide, and/or antibody in a sample from a subject indicates that the subject has or is at risk of developing BPH. In further examples, a therapy is selected for a subject diagnosed with BPH virus, BPH, or risk of BPH, for example, antiviral therapy, 5-alpha-reductase inhibitor, anti-androgen, alpha-1-adrenergic antagonist, gonadotropin-releasing hormone agonist, or a combination of two or more thereof.
 

currer

Senior Member
Messages
1,409
Thanks for posting this Nastasia. No Ive not seen this before. Paprotka and "XMRV" will not account for this.

So this is a patent. But why has not O'Keefe published a paper on her research?

maybe no-one will publish it. Or maybe if you know you will find your paper undergoing a forced "retraction" you dont bother publishing.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
But we have already read something about O'Keefe's research into BPH haven't we Currer? We did know that she has detected a retrovirus in BPH. I can't remember what we read though.
 

currer

Senior Member
Messages
1,409
Yes. This is ME in action isn't it! I used to have a completely reliable memory - for detail especially.

Now if I need to recall something it's often just a blur. It does not seem progressive though (or am I just reassuring myself)
I cant remember anything about my posting about this patent before. I may have missed some of this story - I have been busier lately. I have checked the links you put up and some I have read before, and some not - like this excellent one from asleep -

"I feel like O'Keefe has broken this thing wide open. The VP62 creation story was always a tricky ploy that required prevention of new, sufficiently divergent sequences from surfacing, which O'Keefe seems to now have provided. She has rendered Coffin's immaculate recombination moot. All that story telling, down the drain.

The timing is good too, as the Lipkin study will look foolish if it doesn't take this new information into account.

It would be interesting to find out if the primers used in all the 0/0 studies would have picked up these new ENV ang GAG sequences that O'Keefe found"
 

currer

Senior Member
Messages
1,409
I have re-read all the posts Bob put up. I can see I posted a lot about it. I cant remember doing any of it - I think I'll go and have a lie down!
 

currer

Senior Member
Messages
1,409
Identification of a novel retrovirus in Benign Prostatic Hyperplasia (BPH)

"However we identified what appears to be increased expression of genes related to an antiviral response. Given the recent findings of a novel virus, XMRV, found in some prostate tumors, we analyzed the BPH affected tissue for viral infection. We found that the majority of tissue from symptomatic BPH patients contained low levels of a virus not previously found in humans. Sequencing confirmed that the virus consists of 2 variants, is not XMRV, and likely produces a protein that has been related to inflammation in other species. Interestingly, the exact virus sequence differs among patients, suggesting that upon infection of the tissue, the virus undergoes replication. Furthermore, sequencing revealed that the virus is likely transcriptionally regulated by androgens, which is consistent with the fact that cell growth in BPH is androgen-dependent and the classic non surgical treatment for BPH is inhibition of DHT (an androgen) production. Both variants of the virus have submitted to the USPTO as a provisional patent, as they may be a therapeutic target for this disease."

http://www.upmc.com/Services/urology/experts/research-faculty/Pages/denise-s-okeefe.aspx
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Yes. This is ME in action isn't it! I used to have a completely reliable memory - for detail especially.

I have re-read all the posts Bob put up. I can see I posted a lot about it. I cant remember doing any of it - I think I'll go and have a lie down!

If it's any consolation for you Currer (it probably isn't), I was exactly the same with the Hanson paper yesterday...
I couldn't remember if Hanson had published her paper, and then I discovered that, not only had I posted frequently all the way through the Hanson paper thread, but I had analysed the results in detail!
:eek: :confused: o_O :( :ill:
 

anciendaze

Senior Member
Messages
1,841
I have re-read all the posts Bob put up. I can see I posted a lot about it. I cant remember doing any of it - I think I'll go and have a lie down!
I think that is itself diagnostic for cognitive deficits. The need for the lie down to think clearly is almost pathognomonic.

I've just checked again to see if O'Keefe's BPH research has been published. It has not. While searching I found some interesting work on epigenetic control in prostate cancer. Keep this in mind when you read about genes affected by retroviruses.
 

currer

Senior Member
Messages
1,409
I've had my lie down now.

Yes, anciendaze you are right. Having to lie down and rest so that you can think - that is characteristic of this disorder.
I wonder why it works?

But to get back to the discussion - does anyone think that Lipkin will take the O'Keefe sequences on board?
Saying there is nothing - when these variants have been found - would look very suspicious - like deliberately looking in the wrong place.

Or do you think - they are separating prostate cancer from "CFS" and will pursue retroviral research in PC but not in us?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
...does anyone think that Lipkin will take the O'Keefe sequences on board?
Saying there is nothing - when these variants have been found - would look very suspicious - like deliberately looking in the wrong place.

Lipkin isn't actually doing any research of his own in the XMRV study.
It's up to Mikovits and the other researchers to use whatever methodology and primers they want to use.
Lipkin's results won't be the final word on HGRV's in ME patients, although I imagine that many will see it that way, and a negative result will mean that much of the research funding dries up.

Lipkin's CFI pathogen study (his next big ME study) will use next generation sequencing, and so if there are any HGRVs present in the investigated tissues, then they should show up, in theory.


Or do you think - they are separating prostate cancer from "CFS" and will pursue retroviral research in PC but not in us?

There haven't been any more positive prostate cancer studies, than there have been positive ME studies (if we include the Hanson study as a positive study). It's just that ME has got much more attention because of the WPI and Mikovits. I don't know if there might be more retrovirology research into prostate than ME in the future, but any potential positive results in prostate cancer research will be transferable to other areas of HGRV research.
 

anciendaze

Senior Member
Messages
1,841
One study by Singh used FISH (Fluorescence In-Situ Hybrization) to find prostate cancer (PC) cells with characteristic epitopes. It would not likely be affected by nucleic acid contamination. It was finding some kind of marker associated with PC. Anyone heard of a follow-up, or has all productive research on PC been shut down? The Stieler/Fisher paper seemed satisfied with moving a great deal of PC research back to square one.
 

RustyJ

Contaminated Cell Line 'RustyJ'
Messages
1,200
Location
Mackay, Aust
I don't know if there might be more retrovirology research into prostate than ME in the future, but any potential positive results in prostate cancer research will be transferable to other areas of HGRV research.

Is this a prostate cancer study? As far as I know, and certainly in my case, I have all the symptoms of BPH, 50% of males will eventually be diagnosed with BPH over the age of "old". I see this as a me/cfs study. O'Keefe certainly thinks the pathology fits me/cfs. Perhaps this is the real link between one type of prostate cancer and me/cfs.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
Currer, I think that you were right to post this again. As Bob pointed out some people had even forgotten that Hanson had published a paper. It's hard to keep up with what is important as things develop.

The Hanson paper, the O'Keefe discussion on her blog and the work she is doing herself on XMRV shouldn't be forgotten.