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Epstein–Barr virus infection induce chronic fatigue syndrome

heapsreal

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http://www.tandfonline.com/doi/full/10.1080/17513758.2012.704083
2.2. Chronic fatigue syndrome


The literature on CFS is very broad with hundreds of analysis carried out and a rich collection of data, yet the clinical implications of such findings remain uncertain and a unifying, globally accepted, picture of its etiology and pathophysiology is still missing 22. Afari, N. and Buchwald, D. 2003. Chronic fatigue syndrome: A review. Am. J. Psychiatry , 160: 221–236.
[CrossRef], [PubMed], [Web of Science ®], [CSA]
View all references 1818. Dinos, S., Khoshaba, B., Ashby, D., White, P. D., Nazroo, J., Wessely, S. and Bhui, K. S. 2009. A systematic review of chronic fatigue, its syndromes and ethnicity: Prevalence, severity, co-morbidity and coping. Int. J. Epidemiol. , 38: 1554–1570.
[CrossRef], [Web of Science ®]
View all references 2020. Gerritya, R. T., Papanicolaoub, A. D., Amsterdamc, J. D., Binghamd, S., Grossmane, A., Hedrickf, T., Herbermang, R. B., Kruegerh, G., Levinei, S., Mohagheghpourj, N., Moorek, R. C., Oleskel, J. and Snellm, C. R. 2004. Immunologic aspects of chronic fatigue syndrome. Neuroimmunomodulation , 11: 351–357.
[CrossRef]
View all references 2626. Lorusso, L., Mikhaylova, S. V., Capelli, E., Ferrari, D., Ngonga, G. K. and Ricevuti, G. 2009. Immunological aspects of chronic fatigue syndrome. Autoimmun. Rev. , 8: 287–291.
[CrossRef], [Web of Science ®]
View all references 2828. Lyalla, M., Peakmanb, M. and Wessely, S. 2003. A systematic review and critical evaluation of the immunology of chronic fatigue syndrome. J. Psychosom. Res. , 55: 79–90.
[CrossRef], [Web of Science ®], [CSA]
View all references.

Current theories are looking at the possibilities of neuroendocrine dysfunction, virus geneses, environmental toxins, genetic predisposition, or a combination of these. Several researches suggest that EBV, by prompting a chronic immune reaction in the body, might cause CFS. Indeed, the phenomenology reported is consistent with the idea that the syndrome may follow the occurrence of an infection yielding a massive immune response, which, for causes not yet completely clarified, may persist for a long time, although the underlying infection is no longer in course. In fact, a CFS state is usually associated with an abnormal concentration and/or functioning of B cells, T cells and cytokines. Another interesting and robust immunological fact found in patients with CFS is an unusually high (more than 67%) increase of activated CD8+ cytotoxic T lymphocytes with MHC-II activation markers 99. Caligiuri, M., Murray, C., Buchwald, D., Levine, H., Cheney, P., Peterson, D., Komaroff, L. and Ritz, J. 1987. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J. Immunol. , 139: 3306–3313.
[Web of Science ®], [CSA]
View all references 1010. Carlo-Stella, N., Badulli, C., De Silvestri, A., Bazzichi, L., Martinetti, M., Lorusso, L., Bombardieri, S., Salvaneschi, L. and Cuccia, M. 2006. A first study of cytokine genomic polymorphism in CFS: Positive association of TNF-857 and IFN-874 rare alleles. Clin. Exp. Rheumathol. , 24: 179–182.
[Web of Science ®]
View all references 1717. Devanur, L. D. and Kerr, J. R. 2006. Chronic fatigue syndrome. J. Clin. Virol. , 37: 139–150.
[CrossRef], [PubMed], [Web of Science ®]
View all references 2525. Klimas, N. G., Salvato, F. R., Morgan, R. and Fletcher, M. A. 1990. Immunologic abnormalities in chronic fatigue syndrome. J. Clin. Microbiol. , 28: 1403–1410.
[PubMed], [Web of Science ®], [CSA]
View all references. This will be a key point of our speculation.

From a symptomatology viewpoint, fatigue is a common symptom, but CFS is a multi-systemic disease including even post-exertional malaise, unrefreshing sleep, widespread muscle, joint pain, cognitive difficulties, chronic (often severe) mental and physical exhaustion, muscle weakness, hypersensitivity, orthostatic intolerance, digestive disturbances and more.

2.3. The Epstein–Bar virus

EBV is one of the most successful viruses, infecting over 90% of humans and persisting for the lifetime of the person in a non-pathogenic way4
Strictly speaking, EBV is also associated with serious diseases such as the Burkitt lymphoma, but its incidence is irrelevant with respect to its average behaviour, which is the typical outcome from a many-body theory as statistical mechanics. View all notes

3232. Robertson, E. S. 2005. Epstein–Barr Virus , Edited by: Robertson, E. S. Norfolk : Caister Academic Press.

View all references 3333. Young, S. L. and Rickinson, A. B. 2004. Epstein–Barr virus: 40 years on. Nat. Rev. Cancer , 4: 757–768.
[CrossRef], [PubMed], [Web of Science ®]
View all references. The infection can follow different pathways, in particular, it can turn in AIM (in up to 25% cases 88. Buchwald, D. S., Rea, T. D., Katon, W. J., Russo, J. E. and Ashley, R. L. 2000. Acute infectious mononucleosis: Characteristics of patients who report failure to recover. Am. J. Med. , 109: 531–537.
[CrossRef], [Web of Science ®], [CSA]
View all references) or it can simply introduce the virus in the host organism in a non-apparent way.
The virus aims to enter B cells and, if successful, two outcomes are possible. In the first case, the EBV begins a viral replication cycle (the so-called ‘lytic phase’, a common feature of most viral infections), which induces the death of the infected cell, followed by the complete release of new virus particles, which are going to infect other cells; in the second case, a state of latency (latent phase) is established where the ‘disguised’ virus multiplies and stands by inside the cell, while no extracellular phenomena are observed, in such a way that no tackling by the immune system is evidenced.
During the primary infection, the latent cycle and the lytic cycle proceed in parallel and the immune system addresses most of its resources to the lytic cycle of viral replication; the infection can be asymptomatic, have non-specific symptoms, or be so massive to result in AIM. The acute phase can last up to several months and it ceases when the lytic cycle is interrupted by the immune responses or by the virus itself, then, the infection becomes latent and the host becomes a healthy carrier.
The possible persistence of the acute phase, despite a potent immune response against it, indicates that the virus has evolved strategies to elude the immune system. Among the different hypothesis, one has received particular attention 2323. Hsu, D. H., de Waal Malefyt, R., Fiorentino, D. F., Dang, M. N., Vieira, P., de Vries, J., Spits, H., Mosmann, T. R. and Moore, K. W. 1990. Expression of interleukin-10 activity by Epstein–Barr virus protein BCRF1. Science , 250: 830–832.
[CrossRef], [PubMed], [Web of Science ®], [CSA]
View all references: the antigen BCRF15
The BCRF1 antigen is a Lytic Antigen sharing 70% of the human IL-10R, which is the membrane bound receptor for IL-10, see also 32. View all notes

can simulate the signal produced by IL-10 cytokines (which normally prompts leukocytes specialized against small-sized threatening agents, like EBV's antigens) and determine a delay in the immune response. More precisely, the signal from BCRF1 inhibits the production of real IL-10; the lack of IL-10 polarizes the cellular immune response in the activation of a different kind of leukocyte, specialized in fighting against bigger-sized pathogens.
We finally report an interesting study 77. Bharadwaj, M., Burrows, S. R., Burrows, J. M., Moss, D. J., Catalina, M. and Khanna, R. 2001. Longitudinal dynamics of antigen specific CD8+ cytotoxic T lymphocytes following primary Epstein–Barr virus infection. Blood , 98: 258–259.
[CrossRef]
View all references on T-cell responses, in the cases of a relatively brief (2–3 weeks) and of a protracted (4 months) acute phase. Although expansions of antigen-specific T cells were observed in both situations, the T cells reactivity occurred to be broad (i.e. addressed to several, both lytic and latent, antigens) and narrowly focused (i.e. mainly addressed to a singular antigen, the early BMLF1), respectively.6
An investigation on the link between BCRF1 and BMLF1 can be found in 24. View all notes

Summarizing, a significant presence of antigen BCRF1 can determine a delay in the immune response. As a result, the immune activity may take a long time for the clearance of the infection; during this time, the concentration of TK cells remains high and polarizes against BMLF1 antigen as if an internal self-reinforcement has occurred.
 

Marg

Senior Member
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Location
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Wow, good stuff Heaps. I know EVB is my main thing and no would would consider even looking at it until Dr. Klimas. The answer was always everyone over 30 has it and too controversial. I am wondering now why I put up with that answer, and so sick. You guessed it titers off the wall when I was finally checked. Imunivor helped a lot but still some activation until Acyclovir in May. The EVB feeling is now gone but I continue with Immunior and Acyclovir. I am not sure when I will be tested again. Dr. Klimas said at the last testing it was what doctors liked to see. I can overnight blood but I am going to give it a few more months. We are going to win this fight!
 

heapsreal

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Yes, many docs just think positive to igg antibodies is a past infection and dont realise that the virus still reactivates, many think you need igm titres for it to be reactivating which is wrong. plus these types of viruses are known to reactivate in people with compromised immune systems like us. studies show we have poor natural killer cell function and the role of NK cells is to kill viruses and cancer cells.

cheers!!!
 

GhostGum

Senior Member
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Location
Vic, AU
Wasn't there a rituximab rheumatoid arthritis study where EBV was found in bone marrow samples but not active in blood samples? And those found with the EBV had success with the treatment? Will have to try and find that study again but it made me wonder why it was not more heavily discussed because it seemed to make an obvious possible link.

All new red blood cells in the body are produced from bone marrow, so even though EBV might not appear active in a blood sample it could be sitting in marrow activating all the time?
 

GhostGum

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Here it is,

http://forums.phoenixrising.me/inde...atients-predicts-response-to-rituximab.13350/

Already well covered by heaps by the looks. I was thinking maybe activity was flaring the production of red blood cells and the virus/viruses out of marrow but apparent RBC's have a long life span, 120 days and do not increase from activity but apparently it is actually white blood cells which do increase,

http://www.livestrong.com/article/486089-does-exercise-help-produce-blood/

Either way with a latent virus sitting in marrow I assume all your white and red blood cells are compromised? Would be interesting with any future rituximab studies if they could check marrow samples for viruses before and after like the arthritis study.
 

August59

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The only time that EBV creates ImG antibodies during the inial infection. After it is in the boby and became latent and then re-activates there will only be IgG anitbodies. I believe it is when EBV is in the "latent and not the "lytic" state it is essentially acting like a parasite in that cell and is not even causing cell death at this point. It is actually keep the cell alive for its own benefit. Also when it is in this state the body has no idea it is there and is not even mounting any type of an antibody response.
Commercial labs using high throughput testing equipment does a very poor job of giving accurate results, but it is close enough to establish a general trend. Even Dr. Montoya sends his EBV and HHV-6 samples out to be tested at Focus Diagnostics as they set to to due research grade testing instead of commercial grade.
The EBV, CMV and HHV-6 are playing a bigger role in CFS than most researchers believe, especially HHV-6 as it is hard to detect even in research testing environment. It really likes to hang out in the brain to and can cause some nasty nuerofog.
I know there have been studies looking at EBV being the cause of CFS and the results were negative. I didn't hear no fat lady sing, so I do believe that we will see more from these viruses as time goes on.
That was some good stuff heaps and appreciate as always!!
 

August59

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Here is the pdf file for Dr. Lerner's study that he did a few years back. It compares the success rates of different scenario's viruses with respective treatments. He aslo describes some things in laymans terms that was very clear to me before.
 

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  • Lerner study on EBV_HCMV_HHV6 in CFS.pdf
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niall

Senior Member
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Wow, good stuff Heaps. I know EVB is my main thing and no would would consider even looking at it until Dr. Klimas. The answer was always everyone over 30 has it and too controversial. I am wondering now why I put up with that answer, and so sick. You guessed it titers off the wall when I was finally checked. Imunivor helped a lot but still some activation until Acyclovir in May. The EVB feeling is now gone but I continue with Immunior and Acyclovir. I am not sure when I will be tested again. Dr. Klimas said at the last testing it was what doctors liked to see. I can overnight blood but I am going to give it a few more months. We are going to win this fight!

When you say the EBV feeling is gone, does that mean you feel well? What is your activity now and what was it before you started Imunovir? Also, can you please state the dosing protocol for Acyclovir since beginning this treatment? Are you on a low maintenance dose now if full latency has been achieved?
 

Marg

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When you say the EBV feeling is gone, does that mean you feel well? What is your activity now and what was it before you started Imunovir? Also, can you please state the dosing protocol for Acyclovir since beginning this treatment? Are you on a low maintenance dose now if full latency has been achieved?


Yes, gone but still have some FM stuff going on in legs.. first and worst symptom. I don't know how I made the first the trip to Miami I was so sick. I was found to have POTS with a tilt table test so addressing that has helped a lot. I have not had a test to check immune system since the end of May, it was much better at last testing but still some activation so Acyclovir. I take 800 mg twice a day. The feeling was a sick flulike feeling not totally gone until Acyclovir. I no longer have it. My dose of Imunivor is 500mg twice a day and off on the weekend. My scrip was wrtten for a year.

I am taking herbals for the parasites and bacterial found in my small intestine. I am only on day 12 of 20 days then 5 days off and do it again. I have no idea how long I have had it or where it could have come from. I do have a toxic feelng today so something is happening with it. I will test for that after finishing the herbal protocol. I will do the stool test from Metametrix again, it found the parasites. It can be done with or without a doctor's order, my GP here is good about all this.
 

mellster

Marco
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Not surprised at all by this, I'd wager that EBV (or CMV to a lesser degree) is involved in 80%+ of the cases. The chronic activated immune response is what I experienced. In fact I think overall it may be at least partially a good thing that the body is trying so hard and maybe we need to support it in the fight and at the same time also gently help weaning it off from fighting when it mostly cleared it.
 

Marg

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Not surprised at all by this, I'd wager that EBV (or CMV to a lesser degree) is involved in 80%+ of the cases. The chronic activated immune response is what I experienced. In fact I think overall it may be at least partially a good thing that the body is trying so hard and maybe we need to support it in the fight and at the same time also gently help weaning it off from fighting when it mostly cleared it.

Hi Mell,
I did a detox tier in CVAC on Friday. Woooo, it did it. I am going to to it again tomorrow. They said it would help with the toxins from die off.

Are you still going to CVAC?

I one tried acupuncture, it made me hyper I had to sit up on the table. The Chinese doctor had never seen anything like it. I realized later it was stimulating and already overactive part of the immune system...what else?
 

mellster

Marco
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Hi Mell,
I did a detox tier in CVAC on Friday. Woooo, it did it. I am going to to it again tomorrow. They said it would help with the toxins from die off.

Are you still going to CVAC?

I one tried acupuncture, it made me hyper I had to sit up on the table. The Chinese doctor had never seen anything like it. I realized later it was stimulating and already overactive part of the immune system...what else?

Hey Marg - no I am just on MAF314 and methylation/supplements maintenance as I am getting plenty natural exercise again and I changed work places so I am not near the CVAC anymore. It was a good experience though, maybe they will open on right in San Francisco :)
 

Marg

Senior Member
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343
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Hey Marg - no I am just on MAF314 and methylation/supplements maintenance as I am getting plenty natural exercise again and I changed work places so I am not near the CVAC anymore. It was a good experience though, maybe they will open on right in San Francisco :)

They are doing more studies, all secret, don't know what they are up to.
I cannot do anything more until rid of the parasites. That is how I found out, the second methylation test was not as got as the first. So I had more testing and all this came out of it. So until I am tested again for parasites I am off methylation, I do get a b complex injection to bypass the critters.

How is the little guy, bet no so little any more.

Some football players from a college here are going to CVAC, they love it. I asked one what he felt in time and he said he could run longer and not run out of wind, more endurance in all things football. They are such good shape anyway and this gives them an edge.
 

alex3619

Senior Member
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13,810
Location
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EBV is one of a number of pathogens that goes from latent to active in inflammatory zones. So it can dump live virus from B cells into the brain or gut lining if they are inflammed. If inflammation continues, then dumping of latent virus will continue. This is perhaps one reason why it keeps reactivating. Bye, Alex
 

niall

Senior Member
Messages
100
Location
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Yes, gone but still have some FM stuff going on in legs.. first and worst symptom. I don't know how I made the first the trip to Miami I was so sick. I was found to have POTS with a tilt table test so addressing that has helped a lot. I have not had a test to check immune system since the end of May, it was much better at last testing but still some activation so Acyclovir. I take 800 mg twice a day. The feeling was a sick flulike feeling not totally gone until Acyclovir. I no longer have it. My dose of Imunivor is 500mg twice a day and off on the weekend. My scrip was wrtten for a year.

I am taking herbals for the parasites and bacterial found in my small intestine. I am only on day 12 of 20 days then 5 days off and do it again. I have no idea how long I have had it or where it could have come from. I do have a toxic feelng today so something is happening with it. I will test for that after finishing the herbal protocol. I will do the stool test from Metametrix again, it found the parasites. It can be done with or without a doctor's order, my GP here is good about all this.

Thank you for your informative response and I'm happy you are improving. I may start either Acyclovir or Famvir pending the results of blood drawn on August 6th. After ten months on Ampligen, my energy has improved and I feel less sick but I still have to be careful not to do too much. Judging from my continued symptoms, I feel the EBV & HHV6 levels are still high. I wonder if there is much difference between Acyclovir and Famvir.
 

Marg

Senior Member
Messages
343
Location
Wetumpka Alabama
Thank you for your informative response and I'm happy you are improving. I may start either Acyclovir or Famvir pending the results of blood drawn on August 6th. After ten months on Ampligen, my energy has improved and I feel less sick but I still have to be careful not to do too much. Judging from my continued symptoms, I feel the EBV & HHV6 levels are still high. I wonder if there is much difference between Acyclovir and Famvir.

It sounds like you still have activation. I do not know if there is mych difference. Dr. Klimas said it was not as toxic as others was cheap and got the job done. I had a little GI stuff the first week or so and no I do not even know I am taking it.
 

Marg

Senior Member
Messages
343
Location
Wetumpka Alabama
EBV is one of a number of pathogens that goes from latent to active in inflammatory zones. So it can dump live virus from B cells into the brain or gut lining if they are inflammed. If inflammation continues, then dumping of latent virus will continue. This is perhaps one reason why it keeps reactivating. Bye, Alex


I never knew that. How can it ever be stopped or can't it? I know it is not doing much of anything if anything now. This is my second time with it. I just did not know it the first time and no one would check for it. I had a hunch that was it.
 

alex3619

Senior Member
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Logan, Queensland, Australia
There was a paper I read just recently that discusses latent pathogens dumping into inflammatory sites. The list of pathogens? Like a whos who of possible ME causes. If I find a link I will add it. Its about latent pathogens in the blood. As the blood passes through inflammed tissue, they wake up. They then leave the blood cells and go infect something.

Its possible to stop it I think, but we haven't done enough real research. I was discussing a Pied Piper strategy with someone online: antivirals plus careful inflammatories, plus rituximab, could lure latent pathogens out, kill em, and give em no place to hide, though herpes viruses do hide in nerves.

Bye, Alex


the link: http://arthritis-research.com/content/7/2/74/abstract
Full text is available, as is PDF.
 

heapsreal

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