Other possible human retroviruses

[Bob]

anciendaze asked me to post this for him because he is coping with a crisis unrelated to ME/CFS and didn't have time to write it up properly... he also says he may not have time to answer questions... there's also a few words of my own, taken from another discussion thread that i've linked to...

So this is anciendaze's research, and mostly his words, not my own...

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I have been digging into past retrovirus research to see if there have been other possible human retroviruses which have caused research disputes similar to the ongoing XMRV/PMRV drama, and this is what I found...

There is a recent publication about a possible new retrovirus called the Human Mammary Tumor Virus (HMTV) which has 85-95% homology to the mouse mammary tumor virus (MMTV). This is stronger evidence than anyone has produced in the past.

Research Paper, dated May 2010:
http://onlinelibrary.wiley.com/doi/10.1002/cncr.25179/full

Discussion thread, re HMTV:
http://www.forums.aboutmecfs.org/sh...trovirus-in-breast-cancer&p=137155#post137155

This study has detected viral sequences of the HMTV virus, in inflammatory breast cancer (inflammatory breast cancer is a subset of breast cancers), in 71.5% of women in the USA, and in 73.7% of women in Tunisia. Normal breast tissue, tested as the healthy controls, tested at 1.4% positive for the viral sequences.

So, with this research paper published, it looks like this is not one of those 'rumour viruses' that's going to disappear into oblivion...
This research paper has shown that there is consistency in detecting this retrovirus in humans.

It looks like a very significant development.

The authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of American women. These sequences were not found in normal breasts or other tumors. A whole proviral structure was detected in 2 tumors. Breast cancer cells in culture were shown to contain and shed betaretroviral particles. This virus was designated human mammary tumor virus (HMTV). The authors have investigated the presence of HMTV sequences in a variety of breast conditions and geographic locations. Here they report that inflammatory breast cancer from American women shows a higher incidence of viral sequences (71%) than sporadic breast cancers. Similar incidence has been found in inflammatory breast cancers from Tunisia, and in gestational breast cancers. Because these conditions represent highly invasive malignancies, it is concluded that HMTV is sometimes associated with a particularly malignant phenotype. Cancer 2010;116(11 suppl):2741–4. 2010 American Cancer Society.
http://onlinelibrary.wiley.com/doi/10.1002/cncr.25179/full

I have also been told that a researcher at WPI is concentrating on a virus associated with inflammatory breast cancer.

HMTV is a betaretrovirus So there maybe a real chance a beta retrovirus is lurking in humans.


Going in another direction, I looked at problems in detecting bovine leukemia virus, a delta retrovirus.
http://dial.academielouvain.be:8080/vital/access/manager/Repository/boreal:21617?site_name=UCL
http://dial.academielouvain.be:8080/vital/access/services/Download/boreal:21617/PDF_01?view=true

The bovine leukemia virus is widespread in cattle, and will almost certainly infect primates.

This led me to think about the goat's milk at the center of the Lyndonville outbreak.

Dr. David Bell investigated an outbreak of apparent ME/CFS among children in Lyndonville, NY on his own. He found those at the center of the outbreak had all drunk cocoa made with unpasteurized goat milk. Samples from these cases went to DeFreitas lab. at Wistar, where she found similarities to previous work she had done on an apparent MS outbreak in the Florida Keys. She associated this with HTLV-like sequences, which only says it was a delta retrovirus, not HTLV-I or HTLV-II. (This didn't stop other scientists from testing for HTLV-I and II, which then discredited her work when they couldn't detect anything.)

Several aspects of this work differ from recent work on XMRV. Judy Mikovits has said DeFreitas virus was definitely not XMRV. What was it, or at least the C-type virus with a diameter of 70 nm. in those pictures? One candidate I considered was bovine leukemia virus, which is widespread in cattle, and offers familiar problems for detection. It is also likely to involve recombination.

Poking around the data from the MS outbreak in the Keys, I noticed it took place among nurses at a hospital on Stock Island, named because it once housed a slaughterhouse serving Key West. This yielded a possible sequence of vectors: cattle => rats => cats => nurses

In subtropical regions, where winter does not eliminate diseased animals, it is entirely possible for an epizootic to persist for decades. Several of the nurses kept Siamese cats. This doesn't prove anything, but it is a line for investigation. I believe people have followed up, but have avoided publishing because of prejudice over DeFreitas' work.


Taken together, Bovine Leukiemia Virus, DeFreitas's virus, HMTV and XMRV/PMRV would point to the possibility of beta, delta and gamma retroviruses being in the blood supply.


There is other evidence that beta and gamma retroviruses may have been in human populations for some time without being detected, and there has been controversy over such basics as copy numbers. Here's an article on a delta retrovirus, widespread in cattle (BLV), which explains the virus's 'strategy' for avoiding detection.
http://dial.academielouvain.be:8080/vital/access/services/Download/boreal:21617/PDF_01?view=true

This extract explains how, and why, these retroviruses are so difficult to detect:

Repression of viral expression is a major strategy developed by retroviruses to escape from the host immune
response. The absence of viral proteins (or derived peptides) at the surface of an infected cell does not permit
the establishment of an efficient immune attack. Such a strategy appears to have been adopted by animal
oncoviruses such as bovine leukemia virus (BLV) and human T-cell leukemia virus (HTLV).
http://dial.academielouvain.be:8080/vital/access/services/Download/boreal:21617/PDF_01?view=true

This is relevant to HTLV, another delta retrovirus found in some human populations.
Is there a human virus resembling BLV? This would explain part of Elaine DeFreitas' findings.

At this point, I believe we are talking about beta, gamma and delta retroviruses which are now in human populations, largely without being detected. This is not simply a problem connected with ME/CFS; there is a faulty assumption in most techniques for detecting retroviruses.

 

[Bob]

And here's a bit more info from anciendaze, that he asked me to post...
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It turns out a delta retrovirus is widespread in cattle, bovine leukemia virus. There are significant problems in detecting this, because it works hard to avoid detection by bovine immune systems. (Cattle can survive unsanitary conditions which would devastate humans.)
http://dial.academielouvain.be:8080/vital/access/manager/Repository/boreal:21617?site_name=UCL

Here's a pertinent quote:

Although several species can be infected by inoculation of the virus, natural infection occurs only in cattle (Bos taurus and Bos indicus), water buffaloes, and capybaras. Sheep are very susceptible to experimental inoculation and develop tumours more often and at a younger age than cattle. A persistent antibody response can also be detected after experimental infection in deer, rabbits, rats, guinea-pigs, cats, dogs, sheep, rhesus monkeys, chimpanzees, antelopes, pigs, goats and buffaloes.

From the same document:

In regions where blood-sucking insects occur in large numbers, especially tabanids, these may transmit the virus mechanically.

The most common tabanids are called horse flies. The blue-tailed fly of song is one common in the southeastern U.S.

It is hard for me to imagine that BLV infection is not in some humans. This would make four classes of oncogenic human retrovirus: beta, gamma, delta and lenti.

Do you wonder there is concern over the blood supply?

 

[Bob]

And now I'm posting for myself again, in my own words... (sorry for any confusion!)

I found anciendaze's information on this fascinating...

Personally, I think that we might just be scratching the surface of human retroviral infections... I think it might turn out that there are loads of them but, like you indicate, they are so difficult to find...

With the viruses that anciendaze has mentioned, above, and the 'rumour' viruses that have been written about, i wonder if there are many many more human retroviruses waiting to be discovered, which will be shown to be linked to many various human diseases and auto-immune diseases.

It seems that scientists have known, since the 1970's at the latest, that the xenotropic MLV's (mouse retroviruses), that we are so familiar with now, have been able to infect human cells...
http://jvi.asm.org/cgi/content/abstract/16/4/844
http://www.retrovirology.com/content/3/1/67

When Jay Levy did his initial work on xenotropic MLV's in the 1970's, I think that he knew, then, so many years ago, that the xenotropic virus/viruses he was investigating could infect human cells, and yet we have only just discovered XMRV.

"Jay Levy studied New Zealand black mice with auto-immune disease and discovered an endogenous MLV strain that could infected human and rat cells but not murine cells. He coined the term 'xenotropic' for viruses that only infect foreign species"...
http://www.retrovirology.com/content/3/1/67

So, like anciendaze, I was wondering if maybe human retroviruses are far more widespread in the human population than scientists dare admit.

I also never forget DeFreitas' virus. If i remember correctly, she saw it 'budding', so it was not just a case of a false PCR reading (but I can never remember the details about her work). I believe that Judy Mikovits said that she wanted to find DeFreitas' virus, so I wonder if she has been looking for it at all, yet, alongside all the other research work she is doing.

 

[caledonia]

Great stuff, thanks for posting. I wouldn't be surprised either to find out that there are lot more retrovirus in humans causing cancers and neuroimmune diseases.

 

[camas]

Thanks for compiling all this info, Bob and anciendaze. This is the first I've heard of either HMTV or BLV. I hope the research into both is ongoing.

I grew up around cattle and horses and was bit more than a few times by horse flies. (It's not something you easily forget since it hurts like hell.) I don't think it's a stretch to think that there are probably some humans infected with BLV.

 

[anciendaze]

viral 'strategies'

Just a quick note between problems:

When we talk about viral strategies, we are not talking about deliberate actions, these are things which work for the virus, and are found by mindless trial and error.

The one strategy discussed above was to avoid expressing molecules which will attract the attention of the immune system on the surface of infected cells.

A second strategy appears to be a large amount of sequence variation, (to the point different researchers are not sure they have the same virus.)

A third strategy appears to be slow replication, with low copy numbers.

It is even possible viruses are recombining with host cell sequences, so that an immune response directed at the virus will hit many other things vital to survival.

All of these strategies also make the job of researchers more difficult. If they insist that a viral infection must behave like, say, measles, they aren't going to find sophisticated viruses. The similarity of sequences from XMRV and HERV sequences in human genomes tells me these viruses, or close relatives, have been around for a long time.

You can say the same thing about influenza, but there are still dangerous new strains appearing every decade or so. I believe the ME/CFS outbreaks in the 1980s were new strains. My own infection likely took place much earlier.

When I get time, I want to reexamine the possibility one piece of the puzzle is a delta retrovirus, not just a gamma retrovirus. I'm starting to think viruses pay less attention to these distinctions than we do.