Don't Miss Celia Farber on AIDS Research Corruption in the March Issue of Harper's

The HHV-6 Paradigm

HHV-6 in Bronchiolitis Obliterans Syndrome

"Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation." A new study has found evidence to "warrant further studies to elucidate a possible causal link between HHV-6 and BOS."

Online debate about HHV-6A being the cause of AIDS

A interesting debate about HHV-6 has started among AIDS dissenters.

Human Herpes Virus 6 variant A (HHV-6A) directly linked to multiple sclerosis-like illness.

Evidence Presented at American Neurology Association
Annual Meeting

SAN DIEGO, Oct. 5, 2005 (PRIMEZONE) -- Dr. Claude
Genain of the University of California San Francisco
Medical Center presented evidence at the American
Neurology Association Annual Meeting this week that
shows a direct link between human herpes virus 6
variant A (HHV-6A) and a multiple sclerosis-like
illness.

Dr. Genain injected common marmoset monkeys with HHV-6
variants A & B. Most notably, only infection with
HHV-6 variant A resulted in illness. The monkeys
developed lab evidence and signs of chronic autoimmune
demyelination of the central nervous system, the
hallmark of multiple sclerosis. This is the first time
that any animal infected with HHV-6A has developed
clinical pathology of the central nervous system, and
the most direct evidence to date of a possible causal
connection between HHV-6A and multiple sclerosis.

Dr. Genain's marmoset developed weight loss and
paralysis with sensory deficits after exposure to
HHV-6A. Inflammatory lesions of the central nervous
system and evidence of demyelination were seen on MRI
and microscope slides of the brain tissue. However,
the important finding of the study was direct evidence
of the presence of HHV-6 viral antigen within the
nerve cells of the brain stained with an
HHV-6-specific antibody.

HHV-6 variant B (HHV-6B) causes roseola, a
self-limited fever and rash, in over 95% of young
children by age 2. After the initial illness, HHV-6
persists indefinitely in its quiescent, latent form in
the cells of the central nervous system, bone marrow
and immune system. However, HHV-6 can reemerge and
actively replicate later in life, producing new virus
particles that can cause illness. HHV-6 can reactivate
in immunosuppressed patients and cause life
threatening complications, such as opportunistic
infections and encephalitis, in post-transplant
patients.

The quest for a theory of viruses as a causative agent
for multiple sclerosis and other diseases has long
eluded scientists. A direct link between infection
with HHV-6A and multiple sclerosis has been lacking
until now.

According to Dr. Genain, "For the first time,
scientists will be able to look into the biological
process leading to multiple sclerosis at its very
beginning, when no one suspects the disease and people
have not yet experienced its symptoms." In recent
years there has been a considerable degree of interest
in the relationship between HHV-6A and multiple
sclerosis, because HHV-6A DNA has repeatedly been
found in brain tissue and the cerebrospinal fluid of
affected patients, and increased levels of antibodies
to viral antigens in their blood only present during
replication of HHV-6A are frequently detected.

A comprehensive analysis presented by Dr. Dharam
Ablashi, co-discoverer of HHV-6 and Scientific
Director of the HHV-6 Foundation, at the International
Fatigue Conference on Fatigue Science held during
February 2005 in Osaka, Japan, discussed all clinical
studies published in the medical literature on the
association between HHV-6A and multiple sclerosis.

His summary of the existing literature demonstrates
that when lab methods detecting the presence of active
HHV-6A infection are used, an exceptionally strong,
statistically significant association between HHV-6A
and both multiple sclerosis and chronic fatigue
syndrome (CFS) is consistently seen. Lab methods that
detect latent HHV-6A virus are not able to
consistently identify either MS or CFS patients.

Having an experimental animal model linking HHV-6A
infection to central nervous system pathology will
open the door to new types of research investigations.
The common marmoset has a well-known propensity to
develop experimental autoimmune encephalitis, a
chemically-induced animal model of multiple sclerosis
that is commonly used when investigating the efficacy
of new MS drugs. The inflammatory demyelination of
nerve cells in a live primate model after exposure to
the HHV-6A virus has now been demonstrated for the
first time. This marmoset model will add a new
dimension to the drug discovery and development
process for multiple sclerosis.

Dr. Ablashi, who has published numerous medical
studies demonstrating the causative role of human and
primate herpes viruses in various types of lymphomas
and leukemia, commented, "Nonhuman primates are
genetically closest to man. Dr. Genain's pathogenic
model of HHV-6A infection in the common marmoset will
enhance our understanding of the role that the HHV-6A
virus plays in the induction of typical MS lesions.
This model will be very important in the study of the
disease process, and evaluation of new molecules that
can prevent active HHV-6A viral infection and the
development of multiple sclerosis."

Dr. Genain's work was supported by grants from the
HHV-6 Foundation, Multiple Sclerosis Society, Cure MS
Now, DANA Foundation and Lunardi Foundation.

Gallo on HHV-6

Here's what Robert Gallo had to say about HHV-6 in an
NIH interview in 1995:

Have we ever argued for a possible cofactor? Yes, with
the qualification I just told you, that it is obvious
that some things will promote progression and some
things will inhibit progression. One of those things
may be the genetics of me versus you. We can say dose
is a factor that can lead to progression, or lack of
it, and at a greater or lesser rate. But we have
argued for certain herpesviruses as possibly being a
factor in promoting AIDS progression. Several groups
have argued for cytomegalovirus because it does do
things and it does activate more HIV in some subtle
settings.

In the middle of the 1980s, we became aware that the
lymphomas that were associated with HIV infection were
perhaps one-third of the time EBV-positive.
Epstein-Barr virus, as you know, can immortalize some
B cells and, when you have EBV-positive lymphomas,
generally they are the kind of lymphomas that, more or
less... If they do not require EBV, EBV makes the
probability of getting a lymphoma much greater,
because the cell cannot die easily. It is
immortalized. Other genetic events are needed to
develop the lymphoma, but the immortalization of the
cell is perhaps a key factor that makes it probable
that it will be an EBV-containing cell that is the one
that will become a lymphoma.

What about the two-thirds of lymphomas in HIV-infected
persons that were not EBV-positive? We wondered if
there were herpesviruses yet to be discovered. We
looked in the B-cell lymphomas of patients with AIDS
who were negative for EBV and we discovered the first
new herpesvirus in 25 years, and the first herpesvirus
of man that targeted predominantly the T cell.

We had a new herpesvirus, but it was not involved in
the lymphoma, at least not as far as anybody knows,
even today. We even misnamed it. We called it HBLV,
because we found it in a B-cell lymphoma. Then we
studied it more intensively and determined that it
primarily infected T cells, not B cells, which was an
unexpected finding. We learned that it killed T cells
when it replicated. Then we learned that it infected
natural killer cells and, when it did so, it made
those cells attack other natural killer cells. We
learned that it could infect the same cell as HIV and
activate HIV expression. Next we learned that it
infected CD8 cells and activated the gene for CD4, the
only known biological agent I am aware of that
activates the gene for CD4. Now, the CD4+/CD8+ cells
could be targets for HIV.

It was at that stage we proposed that the herpesvirus
might be a cofactor for progression of AIDS. It was
then that I started to be careful of the use of these
words and called it a catalyst for progression, that
is, a nonessential cofactor, but something that makes
disease progression go faster and also makes it more
probable that immune deficiency will develop.

We put that idea out and it got a little bit of a
reception by [Dr. Larry] Corey in Seattle, and by [Dr.
Donald] Don Carrigan at Wisconsin. But then [Dr.
Harold] Jaffe published a paper, the data of which we
already had in hand. I think that paper by Jaffe and
his colleagues at the CDC [Centers for Disease Control
and Prevention] was not a sophisticated look at the
problem. Namely, they said, Look, everybody has
antibody, so how can it be a factor in progression?
That is like saying a cytokine like TNF [tumor
necrosis factor] is not important in disease
pathogenesis because everybody has it. The question
is, if 90 percent of the human population has it, they
also have EBV, but EBV can cause Burkitt's lymphoma
under certain settings. The question is, does it get
activated in an immune-suppressed individual?

We put the problem aside for a while because we did
not have a quantitative assay to measure the amount of
herpesvirus; only this antibody that indicated a
previous exposure to the virus, which everybody
showed. We argued, however, when we presented it, that
we needed to have a quantitative assay for virus in
blood and the amount of human herpesvirus-6 [HHV-6]
DNA in lymphocytes circulating around.

At this time we learned of Carrigan's work. He
reported in a few clinical papers, that sometimes in
immune-suppressed people, following transplantations,
he saw an enormous amount of human herpesvirus-6
replication and that he believed it was responsible
for some of the bone marrow abnormalities in such
people. He showed a lot of virus in bone marrow.
Second, he pointed out and emphasized that
interstitial pneumonia is the cause of death in 10
percent of the deaths of HIV-positive people. No one
knows the cause of that interstitial pneumonia, and he
found the lungs of those who died loaded with human
HHV-6. He presented at our laboratory meeting that he
thought it was very likely that HHV-6 was the cause of
those deaths.

Meanwhile, before this, Japanese workers had shown
that HHV-6 was the cause of roseola infantum, also
known as exanthem subitum, a disease of infants, with
fever and rash, but usually with not much more.

So now what is new? I have discussed with my colleague
[Dr.] Paolo Russo that the only way we are going to
get any proof of this, or get stronger support, is if
we get a specific inhibitor that does not inhibit HIV,
inhibits HHV-6, and as far as we know does not inhibit
anything else, is relatively non-toxic, and then show
that patients do better rather than worse.

Another way of doing it would be to find an animal
model not infected with a parallel virus to HHV-6
which can be infected by SIV [simian immunodeficiency
virus]. SIV can induce some immune deficiency–not the
acute sort–but there are monkeys in which SIV induces
nothing, there are monkeys in which some strains of
SIV induce an acute AIDS, and there are monkeys where
some strains of SIV induce a disease more similar to
the human disease, where it takes time.

We used such a system. This is not published data.
With the SIV alone, there was a little immune
deficiency, and with the HHV-6 alone nothing, but with
the two together they got it. I think we have proven
the point with that rhesus virus and that we can
publish that soon. So, I believe human herpesvirus-6
is a factor in AIDS progression.

http://history.nih.gov/NIHInOwnWords/docs/gallo3_01.html

Diabetes Insipidus may also link AIDS and CFIDS

In a recent Co-Cure posting on CFIDS, Rich Van
Konynenburg writes "we know that many PWCs have mild
diabetes insipidus."

The following appeared on the Aegis site which is
devoted to AIDS research:

Int Conf AIDS 1994 Aug 7-12; 10:196 (abstract no.
PB0797)
Harris P, Curry R; AIDS Clinical Research Center of
Washington, DC 20009.

OBJECTIVE: Ten of 200 patients have complained over
the last year of polyuria, polydipsia and nocturia. We
were interested in whether diabetes insipidus (DI) may
be directly associated with this infection.

METHODS: We measured urine and serum osmolalities,
serum antidiuretic hormone (ADH), serum sodium, BUN,
glucose and potassium levels; calculated serum
osmolalities; evaluated CD4 and CD8 counts, Beta-2
microglobulin and HIV P-24 antigen levels; assessed
recent brain scans; reviewed clinical pictures and
noted current medications.

RESULTS: ADH levels were less than 1 pg/ml, serum
osmolalities 295-312 mos/kg H2O, CD4 levels 3-564/cmm,
CD8 levels 86-1186/cmm, Beta-2 microglobulin levels
3.5-5.6 mg/l. Five had reactive HIV P-24 antigens.
Seven had essentially normal MRI's (3 not done).
Medication and secondary infection did not account for
DI.

DISCUSSION AND CONCLUSIONS: That 5% of our patients
have primary central diabetes insipidus suggests DI
may be an underestimated complication of HIV
infection.

English CFS Activists are Helping to Show that CFS is Related to AIDS

In England, patients with CFS have been under attack
by an aggressive group of psychiatrists who are
determined to prove that CFS is a psychiatric
disorder. It has been a very nasty battle and has
given a great deal of impetus to scientific attempts
to show that CFS is a real physiological illness. As
with most CFS research that has been done in America,
the more serious the research in England gets, the
more it seems to suggest that CFS is part of the AIDS
epidemic. The newest research showing that CFS is a
disease of oxidative stress is no exception.

For a couple of decades a few scientists in Australia
known as "The Perth Group" have insisted that AIDS is
a disease of oxidative stress. They have argued that
HIV has never been properly isolated and has not been
shown to be the cause of AIDS. The Perth Group has
tried to show that gay lifestyle factors have been the
source of the oxidative stress.

A new paper published in Free Radical Biology &
Medicine (2005:39:584-589) By Gwen Kennedy, Vance A
Specne, et al. concludes that "Oxidative
stress levels are raised in chronic fatigue syndrome
and are associated with clinical symptoms." Give that
nobody has yet accused CFS sufferers of secretly
conducting gay lifestyles, the Perth Group may want to
reconsider their theories about the source of
oxidative stress in AIDS. No one has yet proposed a
theory that two kinds of oxidative stress--gay and
straight--are causing a very similar epidemic in both
gay and straight people at the same time.

Dr. Neil Abbot (Director of Operations of the charity
MERGE that funded the research) noted on the MERGE
website (www.meresearch.org.uk), "Circulating in the
bloodstream are highly reactive molecules, known as
free radicals, which can cause damage to the cells of
the body, a process called oxidative stress. In
healthy people, increases in free radicals are
neutralised by antioxidant defences, and it is only
when these defences are overwhelmed that cell injury
results. The source of excessive free radical
generation in ME/CFS patients may be associated
with a variety of altered biological processes".

Dr. Abbot also said that the research "suggested that
many patients currently diagnosed with ME/CFS could
have an inflammatory condition and be in a
'pro-oxidant state'".

What's in a name? Everything and more.

AIDS = Inaccurate construct not reflecting reality

CFIDS/AIDS = Better construct reflecting reality

CIDS (Chronic Immune Dysfunction Syndrome) = Best
construct reflecting reality

HAART for AIDS may cause Oxidative Stress

http://www.aidsportugal.com/article.php?sid=3241