HHV-6 Infections: Observations Based on Published Medical Data - Major Findings and Implications
By Alan Cocchetto

Though some people may think otherwise, there is much known about HHV-6
and ME/CFIDS - perhaps more than you thought!  In this article, I will 
discuss some
of these points and observations that I have made based on the scientific data
available thus far.
      Let me begin by mentioning two gems worth reading.  The first is the 
latest
US Patent on HHV-6 from Dr. Robert Gallo and his former team at the National
Cancer Institute. (US Patent # 6,018,027 issued 1/25/2000)  The second is a
publication by Dr. Donald Carrigan and Dr. Konstance Knox titled "In-Vitro
Suppression of Bone Marrow Progenitor Cell Differentiation by Human
Herpesvirus-6 Infections" from 1992.  Why are these important and what can be
learned here?
      First, you have to understand that HHV-6 infection acts by way of a 
'plug and 
socket' arrangement or mechanism.  What do I mean by this?  Well, HHV-6 
(acting
as the 'plug') looks for receptors (the 'socket') in the body to fuse with or 
bind to.  In
the case of HHV-6, this receptor is given the name CXCR4.  In scientific 
terms,
CXCR4 is known as a chemokine and chemokines have specific cellular 
functions. 
Anyway,  HHV-6 'plugs' itself into this 'socket' receptor and begins its 
replicating
journey.  Simple enough in concept!  What is important here is that this CXCR4
receptor is found on T-cells, neurons in the brain and nervous system, and in 
the
bone marrow.  So that is where you see the signs of the infection and this 
is, as you
will learn, a major assault on the body's defense system!  
      Now, let's look briefly at the two papers mentioned above.  First, 
Gallo states 
that HHV-6 infection directly targets neurons and megakaryocytes.  Neuronal 
cells
are found in the brain, central, and peripheral nervous systems.  So that 
agrees with
what has been found scientifically regarding the CXCR4 receptors.  His work
implicates HHV-6 in the direct destruction of neuronal cells!  Next, 
megakaryocytes
are the precursor cells of platelets necessary for coagulation.  This should 
not come
as a surprise either because of David Berg's recent work (Hemex Labs) on
coagulopathies in ME/CFIDS.  
      Returning to HHV-6's ability to target neuronal cells, as in nervous 
system-brain 
infection, should hardly come as a surprise.  Just look at the brain 
dysfunction and
neuropathies associated with ME/CFIDS, MS, and AIDS - all of these pathologies
associated with HHV-6 infection!  More and more medically published data 
points
to a very important 'ring leader' regarding neurotoxicity and neuronal death. 
 In
AIDS, MS, herpes encephalitis, Huntington's, Parkinson's, and other 
illnesses, the
target is a severe neurotoxin called quinolinic acid.  Quinolinic acid 
functions as a
neuronal excitotoxin poisoning neurons. Although quinolinic acid has not been
measured in ME/CFIDS patients with HHV-6 infections yet, we are confident,
based on the medical facts, that it will be found at high levels. The 
National CFIDS
Foundation has contacted several top researchers to pursue this avenue of 
scientific
inquiry since this has not been done and since the data is exceedingly strong 
here.
Interestingly, neopterin level, which has been measured in ME/CFIDS patients
and found to be much higher than normal, has a relationship to quinolinic 
acid and 
neuronal cell excitation.  Why is this important?  Well, let's just say that 
research
exists that shows when quinolinic acid is injected into either the brain or 
the nervous
system - lesions result!  In my mind, this is one of the major targets 
associated with
HHV-6 infections and the resulting neurodegenerative process.
      In the past, much has been reported on the fact that HHV-6 can directly 
target
and kill T-cells.  This too is in agreement with the fact that key receptors, 
such as
CXCR4, are found in these cell types and therefore can be directly infected by
HHV-6.  This should also come as no surprise.  Heck, anyone who has kept 
track of
their lymphocyte profiles over time, using CD4's and CD8's as a measurement 
tool,
will easily recognize the losses here.
      What about Knox and Carrigan's publication on the suppressive effects of
HHV-6 in the bone marrow? (J Infect Dis, 1992 May, 165(5), ‚€œIn vitro 
suppression
of bone marrow progenitor cell differentiation by human herpesvirus 6 
infection‚€) 
What is the implication of this work?  Well, let me first explain that viral 
infections,
especially HHV-6 which can be chronic and so destructive, can lead to 
alteration
and up-regulation of specific cell expression.  Does ME/CFIDS do this?  You 
bet!  
     ME/CFIDS has been shown to up-regulate the expression of tumor necrosis
factor (TNF-alpha) and transforming growth factor (TGF-beta).  Interestingly, 
HIV
infection does the same thing.  The important note here is that the 
overexpression of
either of these factors, over a long time period, leads to suppression of
hematopoietic progenitor cells which leads to alterations in the bone marrow's
ability to 'keep up with the infection!'  This has consequences due to the 
fact that if
the marrow's ability to generate more cells is impaired, the virus is then 
able to
increase its replication and is subsequently able to get the 'upper hand.'  
Knox 
and Carrigan's in-vitro work along with Dr. Paolo Lusso's in-vivo work, done 
in
Italy, both highlight this problem.  HHV-6 suppresses cells in the bone 
marrow's
stromal layer thus altering the body's ability to replenish its cell 
supply-line.  And
since all cells in the human body are ultimately tied to the marrow, this can 
become
a serious life threatening problem.  Of course, CXCR4 is the receptor that is 
found
in the bone marrow!  So this is another major target of HHV-6.
      It doesn't take a rocket scientist to realize some very important 
implications
here.  Major targets of HHV-6 infection are T-cells, neuronal cells of the 
brain,
central, and peripheral nervous systems, and the bone-marrow.  Doctors listen 
up
here!  Any virus capable of directly infecting and thus altering the function 
of these
types of cells cannot be good for you!  Is it any wonder why many of us are 
so very
ill and we are so dysfunctional.  It is about time that doctor's take note 
and find out
these critical facts for themselves by checking on the published literature 
via
Medline since the CDC and the NIH certainly aren't going to tell the whole 
story
yet!  
      Lastly, what are my recommendations at this point?  We are gaining 
knowledge 
very rapidly at this time so please hang in there!  Knowledge is power and I 
believe
this will not only allow us to redefine this illness but will be providing 
important
answers to this very difficult problem from a truly therapeutic perspective.  
Please
see the accompanying research update on HHV-6!


HHV-6: Critical Research Update
By Alan Cocchetto This column is based on new information, just published, by researchers from the US and Italy. The article titled "Multiple Antiviral Activities of Cyanovirin-N: Blocking of Human Immunodeficiency Virus Type 1 gp120 Interaction with CD4 and Coreceptor and Inhibition of Diverse Enveloped Viruses" by Dey B, Lerner D, Lusso P, Boyd M, Elder J, Berger EA. Published in the Journal of Virology, May 2000, pages 4562-4569, Volume 74, Number 10. The lead author Dey and Berger are from NIAID, Lusso is from the San Raffaele Research Institute-Italy, Elder is from the Scripps Institute, and Boyd is from the NCI. In this research article, Cyanovirin, a cyanoprotein derived from a unique species of algae, has been found to offer potent neutralizing activity against HIV via the interaction of gp120 (HIV's envelope glycoprotein) with CD4's (T-cells). Cyanovirin was found to block the gp120-CD4 binding via a CXCR4 mediated interaction. This action is not only vital for HIV's infectivity of these cells but it is critically important to note that the same is required for HHV-6 infections as well. After proving the blocking ability of cyanovirin on the HIV envelope glycoprotein, thus providing newly found capabilities to block the mode of infection of T-cells, the authors proceeded to test the same hypothesis on HHV-6 Variant A Strain GS! As you should recall from the Lake Tahoe outbreak and from work subsequently published by Gallo's group, in 1992 at the NIH, Tahoe people were found to be infected with HHV-6 Variant A Strain GS! No doubt, Dr. Paulo Lusso was key to the testing of cyanovirin on HHV-6A/GS given his extensive background and publications in this area. It was found that cyanovirin critically blocks HHV-6A's capabilities to fuse and infect T-cells. What is noteworthy here is that we have not only found an agent to inhibit the infectiveness of HHV-6A but that the mechanism of action, as to how the binding and infection of these cells work, has been better defined. Both are crutial for understanding how to truly stop HHV-6A, something that is readily apparent here. I also find it interesting that HIV/gp120's mode of infection is the same as HHV-6A/GS! In addition, what is extremely hopeful is that cyanovirin concentrations required for this blocking action are highly specific and therefore the drug concentrations are very small by comparison to currently used agents. (Approximately 2-3 orders of magnitude smaller) What this translates to is that far less drug is required to block the invasion of HHV-6A due to the highly specific nature of the drug. This, of course, translates into far fewer side effects in animal models and subsequently in human patients. And has this been tried in animals - yes, according to the publication and with NO side effects. To quote this paper "The protein is minimally toxic to tissue culture cells; moreover, antiviral concentrations in blood have been achieved and sustained in-vivo in rodents, with minimal toxicity (NCI). Initial studies (NIAID) showing benign effects of cyanovirin in a rabbit toxicity model are encouraging." I would encourage all those who have HHV-6A infections to contact the NIH for additional information regarding the prospects of human clinical trials, which have been mentioned in other papers by NIH researchers. Additional research desperately needs to be conducted here in this critically important area of science. Too many lives have already been lost and many many more are at stake. As CFS patients, we are long overdue some serious help and this may be the true scientific starting point. Lastly, I hope that both Dr. Dey and Dr. Berger happen to drop off a copy of their publication onto Dr. Straus' desk - afterall, they all work at NIAID together and it's obvious that Steve sure could use some serious scientific reading for a change! Go retrieve Gallo's paper, from 1992, Steve, and compare it with this one!?!? Now we are into some very real science that will further our knowledge towards a solution which may finally be in our grasp. This sure beats cognitive behavioral therapy any day!

 
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