JaimeS
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Chronic Epstein Barr Virus...advice?
- Thread starter brittgb
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Hip
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I thought it was too. It seems conceivable that ME/CFS might be caused by certain genetic variants of normal viruses.
For many years now I have wanted to find a commercial testing lab that can genetically sequence all the viruses in my body, using a blood sample or a stomach tissue sample.
If companies like uBiome.com and americangut.org can genetically sequence all the bacteria in your gut using a fecal sample for just $99 (and patients on this forum are taking these microbiome sequencing tests), it should be feasible to the same thing at a similar price for all the pathogens in your blood.
If ME/CFS patients could genetically sequence their viruses for around $99 using some commercial lab, we might start discovering some interesting correlations; ME/CFS patients might have some unusual genetic strain of EBV, enterovirus, or HHV-6, which might be underpinning our ME/CFS.
uBiome and americangut use high-throughput sequencing to genetically identify the bacteria in your gut; high-throughput sequencing was also used by Prof Ian Lipkin in his recent study looking for viruses in ME/CFS.
The great advantage of high-throughput sequencing, or a similar technique called DNA microarray analysis, is that it detects all the viruses present in just one test. If you use regular viral antibody or PCR testing, you need one test per virus, and you will never detect viruses that you are not specifically testing for. Whereas with high-throughput sequencing, you detect all viruses at once in just one test.
It's not clear to me why high-throughput sequencing for blood borne pathogens has not been turned into a cheap commercial test.
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It shouldn't even require anything that complicated - they should be serologically distinguishable by ELISA. If the MS work is replicated, then tests might be marketed for it - and then it would be a simple matter to look and see if such a thing is present in ME. I'm skeptical, but I'm always skeptical. =P I do think the study is very interesting for MS.
Hip
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I don't know the details of it, but I imagine there will be quite a range of different genetic variations of EBV in circulation. The genetic variants associated with MS might not be the same as the variants possibly associated with ME/CFS.
I don't think these sequencing machines are that complicated once the equipment is set up, and they can be used for clinical purposes if necessary. I read one story few years ago about hospital using DNA microarray testing on a patient whose severe infection could not be identified. The hospital had run a number of different tests on the patient for various pathogens, but could not find the culprit.
So the doctor summoned the help of a local university with a DNA microarray testing facility. The results came back a day or so later, and it turned out the patient had a parvovirus B19 infection. If I remember rightly, the hospital was charged by the university in order of $1,000 for the microarray testing. That was a few years ago.
DNA microarrays don't do sequencing - they do something more like SNP analysis, similar to 23andme. (By contrast, full genome sequencing is around $8k right now for a human, versus microarray analysis for under $100). They are very economical though and if mutations are found, are a good way to analyze individual viral strains (you only have to look for polymorphisms at certain positions, the rest will be the same between all the strains).
Genetic testing will revolutionize clinical practice - it has already started to.
$1000 is a lot for microarray testing nowadays - for testing a few bacterial or viral SNP's it could be a $10 test... We test 600,000 human SNP's for under $100. Viral genomes are tiny compared to human genomes. Herpesviruses are not highly variable. They are among the largest DNA viruses (maybe the largest) and have relatively complex genomes and accurate DNA replication. This contrasts with viruses like HIV and HCV which mutate rapidly (this makes it very hard to vaccinate against them, and it means they tend to evolve immunity rapidly to drugs - acyclovir is still effective in the vast majority of HSV and VZV cases, despite being used in the same patient for a lifetime and in many, many patients - contrast with HIV where single agent use usually leads to resistance within a few yrs).
Still, we're getting way ahead of ourselves. We would still need to show that there is some difference in the genetics of EBV in ME patients, and no one has even really begun to show that yet.
If it were just caused by virulent EBV, then one would think that 100% of patients would be helped by ganciclovir and recovery would be nearly complete, but we don't observe anything close to that. Some patients don't even have EBV. So maybe it causes some cases but not others - but again, this causes problems with the issue of similar symptomatology despite different infectious causation, even when comparing viruses that cause completely different syndromes otherwise. This makes me very skeptical.
In rare cases, we have identified the viruses that led to ME, and they haven't been particularly interesting or odd - and in many cases they have been spread and only 1 or a few people develop ME. If it were just more virulent strains, then you would see everyone getting it.
Genetic testing will revolutionize clinical practice - it has already started to.
$1000 is a lot for microarray testing nowadays - for testing a few bacterial or viral SNP's it could be a $10 test... We test 600,000 human SNP's for under $100. Viral genomes are tiny compared to human genomes. Herpesviruses are not highly variable. They are among the largest DNA viruses (maybe the largest) and have relatively complex genomes and accurate DNA replication. This contrasts with viruses like HIV and HCV which mutate rapidly (this makes it very hard to vaccinate against them, and it means they tend to evolve immunity rapidly to drugs - acyclovir is still effective in the vast majority of HSV and VZV cases, despite being used in the same patient for a lifetime and in many, many patients - contrast with HIV where single agent use usually leads to resistance within a few yrs).
Still, we're getting way ahead of ourselves. We would still need to show that there is some difference in the genetics of EBV in ME patients, and no one has even really begun to show that yet.
If it were just caused by virulent EBV, then one would think that 100% of patients would be helped by ganciclovir and recovery would be nearly complete, but we don't observe anything close to that. Some patients don't even have EBV. So maybe it causes some cases but not others - but again, this causes problems with the issue of similar symptomatology despite different infectious causation, even when comparing viruses that cause completely different syndromes otherwise. This makes me very skeptical.
In rare cases, we have identified the viruses that led to ME, and they haven't been particularly interesting or odd - and in many cases they have been spread and only 1 or a few people develop ME. If it were just more virulent strains, then you would see everyone getting it.
Hip
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@Eeyore
Yeah, I know very little about how DNA microarray analysis or high-throughput sequencing work; it's an area I would like to read up about, but with brain fog and limited mental energy, I have to be very careful about where I expend my mental energy, and what I try to read up on and learn. Very annoying really, because I aways loved reading and learning new things.
EBV is not the only potential viral causal factor; Dr Chia thinks enterovirus will turn out to be a major cause of ME/CFS. In 200 consecutive ME/CFS patients, Dr Chia estimated that enterovirus was responsible for 55% of these ME/CFS cases, Chlamydia pneumoniae responsible 9%, and EBV responsible for 3% (see: Table 1. Probable causes of chronic fatigue syndrome in 200 patients). This of course is only very rough guesstimate, but it's interesting.
There does not seem to any research in to the viral strains associated with ME/CFS (apart from this HHV-6 study that found the nastier HHV-6A variant is more strongly linked to ME/CFS).
What I found interesting was that in the case of murine chronic inflammatory myopathy, it is the Tucson strain of coxsackievirus B1 that precipitates this disease (ref: here). In fact if you search PubMed on this subject, you find quite a few studies examining this Tucson strain of coxsackievirus B1, and its ability to cause chronic inflammatory myopathy / polymyositis.
So here is another example of a particular strain of virus causing a disease. Might particular strains of coxsackievirus B be responsible for causing ME/CFS?
Yeah, I know very little about how DNA microarray analysis or high-throughput sequencing work; it's an area I would like to read up about, but with brain fog and limited mental energy, I have to be very careful about where I expend my mental energy, and what I try to read up on and learn. Very annoying really, because I aways loved reading and learning new things.
EBV is not the only potential viral causal factor; Dr Chia thinks enterovirus will turn out to be a major cause of ME/CFS. In 200 consecutive ME/CFS patients, Dr Chia estimated that enterovirus was responsible for 55% of these ME/CFS cases, Chlamydia pneumoniae responsible 9%, and EBV responsible for 3% (see: Table 1. Probable causes of chronic fatigue syndrome in 200 patients). This of course is only very rough guesstimate, but it's interesting.
There does not seem to any research in to the viral strains associated with ME/CFS (apart from this HHV-6 study that found the nastier HHV-6A variant is more strongly linked to ME/CFS).
What I found interesting was that in the case of murine chronic inflammatory myopathy, it is the Tucson strain of coxsackievirus B1 that precipitates this disease (ref: here). In fact if you search PubMed on this subject, you find quite a few studies examining this Tucson strain of coxsackievirus B1, and its ability to cause chronic inflammatory myopathy / polymyositis.
So here is another example of a particular strain of virus causing a disease. Might particular strains of coxsackievirus B be responsible for causing ME/CFS?
JaimeS
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@Hip -- there is a SNP that makes one more susceptible to be 'hit hard' with EBV than other people. The same SNP is documented for resulting in swift progression to full-blown AIDS on infection with HIV. That SNP is rs3732378, and I have it.
Just dxed with EBV myself!
...can you guys believe that despite the family hx I conveyed here, no one had tested me for it, yet?
-J
Just dxed with EBV myself!
...can you guys believe that despite the family hx I conveyed here, no one had tested me for it, yet?
-J
rs3732378 (CX3CR1 T380M) "AG" or "AA" would be the genotypes for the pathogenic mutation in that one, in case anyone wants to look up their results for it.
drob31
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I'm A/G and I just got EBV