XMRV -Cover-up & Contamination Theories

[Guest guest]

http://bit.ly/fYdTHs

In January 2011, I began to work for the WPI, but

the content of this blog does not represent the

institute. It is personal. Any opinions expressed are

mine alone.

Deckoff- MD

````

Sunday, March 6, 2011

Cover-up and

contamination theories

While the days, weeks and months pass, the

scientific community continues to work on what isn't,

instead of what is.

The question of how a lab contaminant produces an

immune response in patients hasn't been addressed

by any of the contamination theorists.

And how do you manage to contaminate the

patients' samples at a higher rate than the controls

when all samples were blinded and run at the same

time?

In fact, it is the patients that are contaminated with

a family of MLV-related retroviruses, not Dr. Mikovits'

lab.

This abstract was presented at CROI a few days

ago:

XMRV Probably Originated through Recombination

between 2 Endogenous Murine Retroviruses during in

vivo Passage of a Human Prostate Cancer Xenograft.

Paprotka (http://bit.ly/h7YizP)

Many questions arise without the full paper, but it

seems that far from showing XMRV to be a lab

contaminant, the study shows what may in fact have

happened.

Human and mouse endogenous retroviruses

recombined through subsequent passages in vivo

(in mouse) to produce a fully replicative xenotropic

exogenous retrovirus, that in fact may prove to be

the most infectious human retrovirus yet.

In animals, similar viruses are communicated

casually.

Lombardi et al demonstrated that this new human

retrovirus is circulating in the blood of as many as 10

million Americans. A public relations nightmare.

So what did the scientists who said this was

impossible do?

First they denied its existence, then tried to suggest

results were the result of mouse parts in their

reagents, but none of the arguments have in any

way refuted the data of Lombardi et al or Lo et al,

who rigorously ruled out contamination.

What they have shown is that it is possible to

produce XMRV in a lab. Like the murine retroviruses,

recombination events produce new pathogenic

variants.

See my post from September 10 about

Ruscetti's work: Lessons from the murine

retroviruses (http://bit.ly/horFJk)

As for the 22Rv1 cell line being the source of XMRV

contamination responsible for the whole mistaken

affair, none of the labs involved in the Science paper

Lombardi et al, have ever used this cell line.

They couldn't have contaminated subjects' blood with

virus produced by a cell line which all three

investigators at different institutions can prove

beyond a shadow of a doubt never entered their

laboratories (personal communication).

Sillier still, is the idea that this supposedly singular

event was the source of infection, since it has only

been around since 1999: A new human prostate

carcinoma cell line, 22Rv1. Sramkoski

(http://1.usa.gov/hWIhz1)

My guess is that passing lots of human tissue

through mice and then culturing in the laboratory for

now more than four decades produced the conditions

to enable a very unlikely event- by giving it many

chances to occur.

A probable place for this to have happened was in

the creation of live attenuated virus vaccines where

virus is made less virulent with multiple passes

through animal cells in tissue culture.

The earliest live polio vaccine was made by

Koprowski using Swiss albino mouse brain cells.

The first dose was administered to a child in 1950.

He also used monkey kidney cells which were

implicated in passing SV40 to humans.

Albert Sabin's live polio vaccine was produced from

attenutated virus obtained from Koprowski.

Mouse cells and the cells of other species have also

been used over the years in the creation of other

vaccines. Some vaccines, including attenuated

Measles and Mumps in the MMR, are grown on duck

and chick embryo cells.

Domestic fowl have endogenous retroviruses, avian

leukosis viruses (ALVs or ASLVs), that do very similar

things to the gammaretroviruses.

Recombination events are involved in pathogenicity

and they can infect the cells of other species in

tissue culture.

XMRV requires the XPR1 receptor to infect cells. The

XPR1 receptor is ubiquitous in mammalian cells.

Lab mice are resistant by virtue of XPR1

polymorphisms. The alpha retroviruses use a receptor

called TVB. TVB is a tumor necrosis factor receptor

that is most likely the avian homolog of a TRAIL

(TNF-related apoptosis-inducing ligands) receptor.

Here is a paper about the receptor:

A Fifteen-Amino-Acid TVB Peptide Serves as a

Minimal Soluble Receptor for Subgroup B Avian

Leukosis and Sarcoma Viruses. Knauss.

(http://1.usa.gov/i7bj6P)

The abstract contains the following sentence:

*This peptide was sufficient not only for binding to

ASLV-B but also for activating viral entry into

mammalian cells that lacked the cognate viral

receptor.*

Here are two recent papers which should be giving

someone pause, but there is no evidence that

anything is changing in the status quo at the CDC.

Head in the sand or worse?

* Endogenous retroviruses as potential hazards for

vaccines. Miyazawa (http://bit.ly/h9KFuJ)

* Isolation of an Infectious Endogenous Retrovirus

in a Proportion of Live Attenuated Vaccines for Pets.

Miyazawa (http://1.usa.gov/eqOpqI)

Beta retroviruses, e.g. mouse mammary tumor virus

(MMTV), may also be present in tissue culture of

murine cells.

The first PubMed paper seems to have been

published in 1948 when the *milk factor* was first

identified on electron microscopy in tumor prone

mice:

A particulate body associated with epithelial cells

cultured from mammary carcinomas of mice of a

milkfactor strain. - Porter

MMTV is a vertically transmitted endogenous

retrovirus that causes cancer when it inserts near an

oncogene.

Vertical transmission of murine breast cancer by

adoptive nursing was demonstrated in 1936 by Dr.

ph Bittner.

It was formerly classified as a simple retrovirus, but

transcribes a regulatory protein similar to HIV, so is

the first complex murine retrovirus identified.

MMTV codes for a superantigen that stimulates T

lymphocytes which in turn stimulate B cell

proliferation.

At puberty the virus enters the mammary glands with

migrating lymphocytes and infects proliferating

epithelial cells.

MMTV can be transferred exogenously or

endogenously through the germ cell line; the later

infection produces virus present in every cell of the

body.

Mice that acquire the infection this way have a

higher incidence of tumors.

In lymphocytes, it may cause a T cell leukemia.

MMTV has an enhancer region in its U3 long terminal

repeat that activates the virus in mammary cells.

It is activated by estrogen and other glucocorticoids,

including progesterone.

It is especially responsive to the synthetic steroid

Dexamethasone which has been used to induce

lactation in the dairy animals.

And a few new MMTV papers:

* Mouse Mammary Tumor Virus Molecular Biology and

Oncogenesis. Ross

http://www.ncbi.nlm.nih.gov.ezlib.ncifcrf.gov/pmc/articles/PMC3026287

- NCI-Frederick Scientific Library - Restricted access)

* Mouse mammary tumor like virus sequences in

breast milk from healthy lactating women. Johal

http://www.ncbi.nlm.nih.gov.ezlib.ncifcrf.gov/pubmed/21365265

- NCI-Frederick Scientific Library - Restricted access)

* Mouse Mammary Tumor Virus in Anti-Mitochondrial

Antibody Producing Mouse Models. Zhang -

http://www.ncbi.nlm.nih.gov.ezlib.ncifcrf.gov/pubmed/21334408

- NCI-Frederick Scientific Library - Restricted access)

* Prolactin-induced mouse mammary carcinomas

model estrogen resistant luminal breast cancer.

Arendt

http://www.ncbi.nlm.nih.gov.ezlib.ncifcrf.gov/pubmed/21276249

- NCI-Frederick Scientific Library - Restricted access)

Gamma retroviruses are used as the backbone for

gene vector therapy. It is known that retrovirus-

mediated gene therapy of SCID-X1 can lead to

leukemia and lymphoma because proto-oncogenes

can be activated as a consequence of vector

integration.

Gammaretroviral vectors preferentially integrate near

transcriptional start sites and CpG islands.

* Insertional oncogenesis in 4 patients after

retrovirus-mediated gene therapy of SCID-X1.

Hacein-Bey-Abina (http://1.usa.gov/go4jd7)

* A novel model of SCID-X1 reconstitution reveals

predisposition to retrovirus-induced lymphoma but no

evidence of gammaC gene oncogenicity. Scobie

(http://1.usa.gov/gYLSSk)

* Murine Leukemias with Retroviral Insertions at

Lmo2 Are Predictive of the Leukemias Induced in

SCID-X1 Patients Following Retroviral Gene Therapy.

Davé (http://1.usa.gov/edJiXU)

Another place for it to have happened or to be

happening, as demonstrated by the Paprotka CROI

presentation, is in the creation of human to mouse

xenografts.

It turns out that by transplanting human tumors into

mice and passing the tissue through subsequent

generations, it becomes possible to establish tumor

cell lines that couldn't be established before.

Also xenografts are used to study tumors, e.g.

specific tumor immunogenicity and response to

treatments.

Why the presumption that the recombination that

occurred in the Paprotka experiment was a unique

event?

They were fiddling with mouse viruses in the lab in

the 1930s. The first outbreak of Epidemic

Neuromyasthenia was in LA in 1934 and involved

hospital staff.

And suddenly the CDC is worried about lab workers

and testing archived specimens. Will they find it? It

would be funny if it weren't so incredibly sad.

Take a look at this fascinating paper that covers a

lot of material including the problems with

xenotransplantation:

The discovery of endogenous retroviruses. Weiss

(http://1.usa.gov/dXhtiC)

Are we to believe this recombination event occurred

only once and that a pathogenic MLV-related human

retrovirus is only produced by one particular cell line?

Told to us by some of the very scientists that said it

was impossible?

Anyone smell a cover-up?

Much easier to destroy a seminal work than admit

that there may in fact be a family of XMRVs. Careful

reading of the Science paper shows that the

monoclonal antibody used to detect XMRV envelope

in Lombardi et al detects all known xenotropic,

polytropic and ecotropic MLVs.

Antibodies made by patients recognized specific

envelope and gag proteins. PCRs were optimized for

sensitivity, not specificity. And quite possibly there

are many other recombinant animal retroviruses

infecting humans as well, created in laboratories and

injected into almost everybody in the industrialized

world, because of arrogance.

Putting it all together, it seems quite plausible that

batches of vaccines containing retroviruses that are

infectious to humans have been going out for over

half a century.

Much of what I've written here has been known but

ignored for a long time. The assumption was made

that endogenous animal retroviruses couldn't harm

people. It's becoming clear that this was a very

incorrect assumption.

So is there motivation for the cover-up

and baseless attacks against Dr. Mikovits?

They cannot attack the data because it is

impeccable. Coffin and Stoye wrote the commentary

in Science. Have they retracted it?

Coffin said at the CFSAC in October 2009 that " This

is as good as it gets... " .

If this were HIV/AIDS, the year would be 1983. We

have much still to learn about human MLV-related

viruses. Is it even remotely possible that the

findings reported in Lombardi et al were the result of

contamination of their reagents?

No more likely than that the retrovirus described by

DeFrietas et al in 1991 was contamination. Had the

CDC done something then, we could have prevented

the autism epidemic and a second generation of

infected people.

Instead they buried DeFrietas' work by withdrawing

all funding.

Deja vu?