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K. Weber kweber at efn.org
Mon Jan 15 00:14:24 EST 1996

	Dear List,
  What I wondered as I mulled over the posting regarding Parvo and 
reactivated Herpes Virus is whether the Parvo had become more virulant or 
whether a Herpes virus or whether another factor such as environmental 
contamination of the water supply, the Hanford long term effects, etc.  
had compromised immune systems so that a virus normally only affecting 
other mammals had moved in.  I think the environmental question is one 
that can only be answered locally.  It took me a day or two to realize 
that I had a housemate from Yachats who had a chronic infection.  She 
didn't get sick until after I made the dog stop biting her.  They 
roughhoused alot.  It's not funny, but I'm wondering whether dogs can get 
Parvo from people?  I will write Dr. Smith.  I've included below an old 
article on Dr. Martin's discovery at USC of another mammalian virus which developed a taste for very sick FM/CFIDS/ME 
patients.  It's presence is a marker in FM/CFIDS/ME.  I'm wondering among 
other things whether list members might know of any difference between FM/CFIDS/ME 
and animal immune systems that would account for infection of FM/CFIDS/ME human
patients by animal viruses.


Here is Dr. Martin's WebSite:


Dr. Martin has added an article on cats inoculated with simian 
cytomegalovirus-derived stealth virus.

  Research Breakthrough in the Study of CFIDS

by W. John Martin, MD, PhD
Professor of Pathology , University of Southern California

	Persistent viral infections have long been implicated in the 
pathogenises of some cases of chronic fatigue syndrome(CFS).  The nature 
of the virus(or viruses) associated with CFS, however, has remained 
enigmatic.  We have cultured a spumavirus from several individuals 
meeting the clinical criteria of CFS as well as from individuals with 
more severe neurological and neuromuscular disease.  Virus has been 
cultured from both blood and cerebrospinal fluid(CSF).  The CSF 
examination has been otherwise normal with no evidence of an inflammatory 
response.  Spumavirus infection should be considered in CFS patients in 
whom the neurological findings suggest a viral encephalopathy.  It is 
proposed that the term "spumavirus associated myalgic 
encephalomyelopathy"(SAME) be used to designate this subgroup of patients.

	Spumaviruses (foamy viruses) are classified as a subfamily of 
retroviruses which are characterized by their cytopathic effect in tissue 
culture.  The foamy cell appearance is caused by both syncytial cell 
formation and by prominent intracytoplasm vacuoles.  Spumaviruses have 
been identified in a wide variety of species, including primates, 
cows, cats, hamsters, and man.  In primates, these viruses can be 
frequently be isolated from brain tissue.  Similar to neurotropic JC 
virus, spumaviruses do not typically evoke an inflammatory response and 
are difficult to detect unless specifically tested for using either 
molecular probes or tissue culture techniques.

	The initial search for evidence of spumaviral infection utilized 
the polymerase chain reaction (PCR).  The PCR primer set was slightly 
different from those used to detect HTLV-I virus.  The PCR assay was run 
under conditions of reduced stringency.  Positive responses were commonly 
seen in CFS patients tested but rarely in normal individuals.  Blood from 
a PCR positive patient gave a cytopathic effect in culrure characterized 
by the formation of syncytial (foamy) cells (figure 1).  Viral particles 
were observed by electron microscopy within the synctyial cells (figure 
2).  The morphological features strongly suggested spumaviral infection.  
Confirmation was obtained in studies showing that both DNA and RNA, 
derived from the infected cells, would react in hybridization assays with 
a spumaviral probe.  Positive spumaviral cultures have been repeatedly 
obtained from several patients over the last six months.  Spumaviruses 
have not been cultured from normal controls.

Clinical Features

	The patient from whom a spumavirus was initially cultured had an 
illness first characterized as probable encephalitis.  Her CSF 
examination, however, was unremarkable with normal protein and glucose 
levels.  Following this acute episode. the patient has had difficulty 
returning to her work as a clinical psychologist.  The patient is acutely 
aware of her cognitive impairment, especially her ability to name items 
and her capacity for short-term memory recall.  [Eds. Note: See the 
August '91 issue of THE CFIDS CHRONICLE PHYSICIANS' FORUM which addresses 
the topic of cognitive dysfunction and rehabilitation in CFIDS.]  She has 
experienced severe fatique and has had to curtail evening and weekend 
social activities.  She has been evaluated by neurologists, 
psychiatrists, endocrinologists, and infectious disease specialists to 
help exclude alternative diagnoses, as required by the CDC case 
definition of CFS.  Spumavirus has been isolated from her blood on a 
total of six occasions as well as from her CSF.
	Studies on this patient have extended earlier work on probable 
viral infection in CFS patients presenting with neurological symptoms.  A 
school teacher with a one-year history of a cognitive disorder 
experienced an acute episode of severe dysphasia (lack of coordination in 
speech and inability to arrange words in an understandable way).  She 
displayed no motor or sensory disturbances and the CSF chemistry was 
entirely normal.  Magnetic resonance imaging (MRI), however, showed 
several paraventricular lesions.  A stereotactic brain biopsy was taken 
from one such lesion.  Histology showed demyelination with significant 
gliosis.  There was no inflammatory reaction.  By electron microscopy, 
viral-like particles were seen.  The morphology of these particles and 
the PCR reactivity obtained with the biopsy sample are consistent with 
spumaviral infection.
	More recently, a tongue biopsy of a CFS patient has been 
examined.  The patient, an ear, nose, and throat specialist (physician), 
had experienced painful "geographic" changes on his tongue.  He 
specifically asked that the tongue biopsy be examined by electron 
microscopy.  This examination revealed viral particles.  Spuma-like virus 
has since been cultivated from the patient's CSF.  The tongue biopsy, 
blood, and CSF were also positive by PCR analysis.  Other patients, on 
whom we have shown either positive PCR or viral cultures have been 
referred with a wide range of clinical diagnoses including postviral 
encephalopathy, polyneuritis with myositis, myelo-radiculopathy, lupus 
cerebritis, atypical multiple sclerosis, etc.
	An important issue is whether spumaviral infection defines a 
sub-set of CFS patients with more severe neuromuscular disease.  Studies 
performed in conjunction with Dr. Paul Cheney indicate that slightly more 
than half of the patients' samples referred for testing have shown 
evidence for probable spumaviral infection.  Similar data have come from 
studies with other clinicians experienced in the diagnosis of CFS.  The 
approximate 50 percent viral culture positivity rate may be an 
underestimate, since the culture system has progressively improved during 
the last year.  This is not meant to imply that all cases of CFS are due 
to spumaviral infection.  There are likely to be multiple causes of 
chronic fatque and CFS, including infections with other agents, toxins, 
etc.  More extensive epidemiological studies are required to determine 
the true prevalence of spumaviral infection in the community and to relate 
this type of infection with disease manifestations.


	The term myalgic enephalomyelitis (M.E.), as commonly used in 
England, Canada, and Australia, has historical support and more clearly 
defines the subset of CFS patients in whom there is either PCR or viral 
culture data consistent with a spumaviral infection.  Since spumaviruses 
do not appear to evoke an inflammatory response, the term 
encephalomyelopathy is probably more appropriate than encephalitis.  With 
these considerations in mind, I have tentatively proposed the term 
spumavirus associated myalgic enecephalomyelopathy (SAME).  This term 
does not exclude the possibility that spumaviral infection may be 
associated with other disease entities.

Future Directions

	One of the major benefits of having cultured a spumavirus 
associated with CFS is the capacity to determine sensitivity to antiviral 
agents.  Infected cells will be exposed to graded doses of the commonly 
available antiviral drugs.  The ability of each agent to suppress viral 
replication will be used to assist clinicians in the design of in vivo 
therapeutic trials.  Additional antiviral agents will be tested as they 
become available.  The various viral isolates will also be examined in 
detail to determine probable species origin.  This may provide some 
insight into the initial cause and mode of transimission of the 
infection.  The pathophysiology of infection also needs to be explored to 
determine if other approaches exist to suppress the damaging effects of 
viral infection.  Finally, alternative diagnostic assays are needed to 
reduce the burden of culture and to facilitate the screening of 
biological products.


	The support and encouragement of Drs. Paul Cheney and Jay 
Goldstein and several outstanding CFS patients is gratefully 
acknowledged.  Funding for these studies was received from received from 
the CFIDS Association.


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