Herpesvirus: HHV-6, EBV, CMV, ...

[Mayordomo]

HHV-6 foundation

Ancient Retrovirus May Contribute to Chronic Fatigue Syndrome, Multiple Sclerosis and Autoimmunity
http://www.marketwire.com/mw/release.do?id=871774
http://www2.marketwire.com/mw/mmframe?prid=409461&attachid=784831

A Protein from a Common Smoldering Virus Linked to Chronic Fatigue Syndrome and Depression
http://www.marketwire.com/mw/release.do?id=871800
http://www2.marketwire.com/mw/mmframe?prid=409465&attachid=784808

[Mayordomo]

David Bell skriver i sin Lyndonville News om HHV-6 och ME/CFS

HHV-6 and ME/CFS
Lyndonville News, Volume 5, Number 3: June 2008
http://www.davidsbell.com/index.htm#Latest
http://www.davidsbell.com/PrintLynNewsV5N3.htm

[Mayordomo]

Virus is passed from parent to child in the DNA
Tue Sep 2, 2008, Reuters
http://www.reuters.com/article/scienceNews/idUSN0244571620080902?sp=true

Universal childhood virus is inherited in DNA
03 September 2008, New Scientist
http://www.newscientist.com/article/dn14658-universal-childhood-virus-is-inherited-in-dna.html

[Mayordomo]

Det finns videos från konferensen om CFS och virus i juni 2008 i Baltimore anordnad av HHV-6 foundation http://www.hhv-6foundation.org/ . Videosarna finns här http://www.scivee.tv/node/7965/video eller via listan nedan.

Here's a list of presentations with links from the International Symposium on Viruses in CFS & Post-viral Fatigue A satellite meeting of the 6th International Conference on HHV-6 & 7 in Baltimore, Maryland, USA Day 4 - June 23, 2008.
   
  They're in alphabetical order according to presenter taken from the main list of presentations at- http://www.scivee.tv/user/5257/video
   
  There are a few presentations missing- Suzanne Vernon, Martin Lerner, Liv Bode, and Birgitta Evengard specifically.
  -----------------------------------------
   
1  -Nora Chapman (Enterovirus Session)
"How does a lytic enterovirus persist and cause chronic disease?"
http://www.scivee.tv/node/7031
   
2  -John Chia (Enterovirus Session)
"The role of Enteroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"
http://www.scivee.tv/node/6991
   
3  -Kenny De Meirleir (Clinician Forum Session)
"Antiviral treatment strategies in Chronic Fatigue Syndrome"
http://www.scivee.tv/node/7029
   
4  -Brigitte Huber (EBV & Other Viruses Session)
"EBV and IFN-a activation of the human endogenous retrovirus HERV-K18 and CFS"
http://www.scivee.tv/node/6864
   
5  -Jonathan Kerr (Microarray Studies Session)
"Gene expression subtypes of Chronic Fatigue Syndrome (CFS)"
http://www.scivee.tv/node/6642
   
6  -Jonathan Kerr (Parvovirus B-19 Session)
"Stress and parvovirus B-19 associated arthritis and chronic fatigue"
http://www.scivee.tv/node/6645
   
7  -Nancy Klimas (Immune Markers & Viruses Session)
"Immune markers in viral reactivation"
http://www.scivee.tv/node/7113
   
8  -Anthony Komaroff (HHV-6 & 7 in CNS Dysfunction Session)
"Overview on HHV-6 and Chronic Fatigue Syndrome"
http://www.scivee.tv/node/6831
   
9  -Kazuhiro Kondo (HHV-6 & 7 in CNS Dysfunction Session)
"Identification of novel HHV-6 latent protein associated with mood disorders in CFS, depressive disorder, bipolar disorder and HHV-6 encephalopathy"
http://www.scivee.tv/node/6833
   
10  -Dirk Lassner (Parvovirus B-19 Session)
"Erythroviral myocarditis and fatigue like symptoms"
http://www.scivee.tv/node/6898
   
11  -Jose Montoya (Clinician Forum Session)
"Role of elevated antibody titers against human herpesvirus-6 and Epstein-Barr virus in predicting response to Valganciclovir in patients with Chronic Fatigue Syndrome"
http://www.scivee.tv/node/7026
   
12  -Daniel Peterson (Clinician Forum Session)
"Antiviral treatment of patients with HHV-6, EBV & Enterovirus: case reports"
http://www.scivee.tv/node/7030
   
13  -Barbara Savoldo (EBV & Other Viruses Session)
"Chronic EBV: Comparison to CFS and the use of autologous EBV-specific cytotoxic T cells for treatment of persistent EBV infection"
http://www.scivee.tv/node/6866
   
14  -Mariko Seishima (Parvovirus B-19 Session)
"Chronic Fatigue Syndrome following human parvovirus B-19 infection"
http://www.scivee.tv/node/6897
   
15  -Keizo Tomonaga (Bornavirus Session)
"Bornavirus infection: mechanisms of virus-induced neurological disorders and possible link to Chronic Fatigue Syndrome"
http://www.scivee.tv/node/7023
   
16  -Marshall Williams (EBV & Other Viruses Session)
"The EBV-encoded dUTPase and immune modulation; implications for Chronic Fatigue Syndrome"
http://www.scivee.tv/node/6865

[Mayordomo]

Daniel Petersons föredragning på 11 minuter ovan: Daniel berättar om att han använder det antivirala medlet cedofovir/Vistide vid HHV-6 infektion. Han har observerat att flera patienter med CFS har kloniska omstuvningar hos T-cellreceptorer (clonal gamma T-cell receptor (TCRγ) rearramgements), som ser som en riskfaktor för en speciell typ av lymfom (lymphoma). Han nämner kromosomt integrerat (chromosomal integrated) HHV-6 virus.

[affa]

PUB MED KAROLINSKA STLM. 1 juli 2010. Departement in Micro och Cellbiologi.

Epstein-Barr virus binder sig till vitamin-D receptor och blockerar virus hanteringen!

Alltså har D-vitaminregleringen via dess receptorer en påverkan  på immunförsvarets reglering och virushantering.

http://www.ncbi.nlm.nih.gov/pubmed/20593215

[Mayordomo]

Ett par artiklar om framgångsrik behandling av ME patienter som har vissa typer av herpesvirus och inga ytterligare infektioner. Den första artikeln beskriver studien. Den andra artikeln beskriver en hypotes för att förklara data. Båda artiklarna går att läsa i helversion gratis.


A Martin Lerner, Safedin Beqaj, James T Fitzgerald, Ken Gill, Carol Gill, James Edington.
Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome
http://www.dovepress.com/subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-c-peer-reviewed-article-VAAT

A Martin Lerner, Safedin Beqaj
A paradigm linking herpesvirus immediate-early gene expression apoptosis and myalgic encephalomyelitis chronic fatigue syndrome
http://www.dovepress.com/a-paradigm-linking-herpesvirus-immediate-early-gene-expression-apoptos-peer-reviewed-article-VAAT

[affa]

America's Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS
by Neenyah Ostrom

Table of Contents

Chapter Forty

"Sunbathing May Make CFS Symptoms Worse
It is being increasingly recognized that exposure to sunlight isn't as good for people as we once thought it was. As scientists document the damage that pollution has done to the ozone layer that surrounds the earth and protects all living things from the sun's harmful radiation, people are being warned that unprotected sunbathing not only increases their chances of developing wrinkles and skin cancer, but may also damage their immune systems.

It is not known for sure how sunlight damages the immune system, but it may be through a process similar to the way skin is hurt by the sun's rays. The ultraviolet light that makes up part of the sun's radiation is known to be able to damage skin cells' DNA, the genetic material that resides in every type of cell. It's possible that immune system cells are damaged that way by the sun, as well.

It's also possible that Vitamin D, a vitamin that people make in their bodies after exposure to sunlight, contributes to the worsening of CFS patients' symptoms. It's been suggested that vitamin D may not be processed properly by CFS patients, and that the resulting chemical imbalance may make their symptoms worse.

In any event, most doctors who treat CFS patients caution them to stay out of the sun.

Dr. Charles W. Lapp, who works with Dr. Paul Cheney in Charlotte, North Carolina, advises his patients to avoid sunbathing.

In a "Self-Care Manual" that Drs. Cheney and Lapp wrote for their patients in 1991, they also advise patients to avoid the sun. They caution that exposure to sunshine "may reactivate herpes group viruses or provoke skin reactions."

Another reason for CFS patients to avoid the sun is that many find that their eyes have become extremely sensitive to bright light, a condition that is called "photophobia." Drs. Cheney and Lapp advise their CFS patients to wear sunglasses to protect their eyes from the sun."

Detta stycke är taget ur Kapitel 40 i denna länk:
http://www.fms-help.com/aids.htm
Min kommentar:
Intressant att Charles lapp och Paul Cheney ger råd att ME-drabbade skall undvika solbad och använda glasögon, eftersom solljuset riskerar att reaktivera virus inom herpesgruppen.
Det förmodas bero på att D-vitaminet inte blir korrekt hanterat av ME/CFS-drabbade och som resulterar i en kemisk obalans och kan därför förvärra symtomen- fritt översatt. Detta är ju även Trevor Marshalls syn på Vitamin D i förhållande till inflammatoriska sjukdomar. 

[Mayordomo]

Antikroppar emot Epstein-Barr virus dUTPase och DNA Polymeras hos en delmängd av ME/CFS-patienter

En ny artikel har nyligen publicerats av Martin Lerner och Ronald Glaser med flera. De har i en liten studie med sex patienter påvisat antikroppar emot proteiner som bildas av Epstein-Barr virus (EBV), då de är i ett "mellanläge" – mellan att vara helt inaktiva eller reaktiverade. Dessa proteiner heter EBV dUTPase och EBV DNA polymeras. Båda är en typ av enzymer med kopplingar till DNA syntesen.

Epstein-Barr virus kan orsaka körtelfeber – även benämnt mononukleos. De flesta smittas, oftast via saliv, av Epstein-Barr virus redan som barn eller ungdom, men färre än hälften blir sjuka. Epstein-Barr virus lämnar aldrig kroppen utan finns kvar vilande i kroppen. Bland den vuxna befolkningen, uppskattas 95% vara bärare av Epstein-Barr virus.

Epstein-Barr virus infekterar bland annat B-lymfocyter, T-lymfocyter, vissa epitelceller och myocyter (muskelceller). B-lymocyter är platsen för latent (vilande) infektion. Viruset kan orsaka cancer av olika typer t.ex. lymfom eller lymfoprofilerativ sjukdom.

Körtelfeber är den vanligaste orsaken till insjuknade i ME (myalgisk encefalomyelit), ibland (något felaktigt) kallat kroniskt trötthetssyndom (CFS). En del tillfrisknar inom första året, men en del förblir sjuka hela livet. Efter två år har 4% av de som ursprungligen insjuknade i körtelfeber fortfarande ME.

Forskarna har nu visat att EBV kan producera "skadliga" molekyler/proteiner, trots att viruset inte ens är reaktiverat ordentligt. Dessa proteiner antas kunna skapa en immunreaktion som ger upphov till ME-symtom.

Virusen reaktiveras endast partiellt. Det innebär att inga nya virus produceras, och patienterna kommer därmed få inte få utslag på blodanalyser för att påvisa viruset (med t.ex. mätning av antikroppar emot viruset eller PCR). Trots detta kan alltså virusen, som finns vilande i cellernas kärnor, ge upphov till att proteiner produceras. Dessa proteiner lämnar cellen och immunsystemet kan sedan reagera på dem.

Epstein-Barr virus tillhör, liksom Cytomegalovirus (CMV) och Herpesvirus 6 (HV6), herpesvirusfamiljen. Martin Lerner har tidigare visat att patienter, som lider av enbart infektion av dessa herpesvirus, i många fall kan bli bättre av antiviraler. Samma framgång finns inte för patienter som dessutom har infektioner av t.ex. Borrelia, Anaplasma och Babesia – kanske för att dessa infektioner i sig kan orsaka ME-symtom.

Man kan spekulera om detta nya fynd kan öppna vägarna för att identifiera de patienter som har partiell reaktivering av Epstein-Barr virus, och därmed också kunna välja ut rätt patienter för behandling och kliniska studier. Det kan också innebära att man inom biomedicinsk på ett bättre sätt kan dela in patienterna i undergrupper. Man kan spekulera i om de positiva resultaten av rituximab-behandling i forskning av de norska onkologerna Øystein Fluge och Olav Mella, i vissa fall kan bero på att produktionen av antikroppar emot EBV dUTPase och EBV DNA polymeras minskar kraftigt, och att halten av dessa antikroppar minskar allteftersom de bryts ned, vilket skulle kunna förklara att det tar några månader innan effekten av rituximab-behandlingen inträder. Rituximab är ett läkemedel som tar död på en delmängd av B-lymfocyterna.

Se nedanstående länkar för forskningsartikeln¹, nyhet i Science Daily² och pressmeddelande av universitetet³, samt en lista på Martin Lerners tidigare publikationer⁴.

 
1. Lerner AM,  Ariza ME,  Williams M,  Jason L,  Beqaj S,  et al.  (2012) Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset. PLoS ONE 7(11): e47891. doi:10.1371/journal.pone.0047891 

2. Science Daily: Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases

3. Ohio State University: Discovery Could Lead to Faster Diagnosis For Some Chronic Fatigue Syndrome Cases

4. List of publications of Martin Lerner



   

[Mayordomo]

Speculation and hypothesis:

As a result of the findings by Lerner et al. [1], one can speculate if the positive results of rituximab treatment in research by the oncologists Øystein Fluge and Olav Mella [2] (in at least some cases) may be due to a substantially reduced production of antibodies against EBV dUTPase and EBV DNA polymerase, when rituximab has killed a subset of B lymphocytes. One can assume that the level of these antibodies in the blood decreases over time due to a limited life span of the antibodies. This could explain that it takes a few months before the symptoms of the patient improves after rituximab treatment commences.

In the study of Fluge and Mella 2/3 of the patients got better during treatment with repeated infusions of rituximab [2]. Do these patients have ME-symptoms due to an immune reaction when antibodies react to viral proteins produced by Epstein-Barr virus? Can this be the reason that no auto-antibody yet has been found?

Maybe the Epstein-Barr virus dUTPase and DNA polymerase enzymes are produced by infected cells, as for example plasma cells, NK-cells, T-cells, myocytes or epithelial cells. One hypothesis could be that EBV residing inside myocytes incease the production of these enzymes as a result of physical activity, and that the immune system later reacts to them, which causes the typical symptom of post exertional malaise. Treatment with rituximab would not remove these enzyme producing EBV viruses, and the enzymes would still be produced, but there would be fewer antobodies to attach to the enzymes and thus the immune reaction against them would decrease.

/Kasper Ezelius, M.Sc., Örebro, Sweden

References

1. Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, et al. (2012) Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset. PLoS ONE 7(11): e47891.
doi:10.1371/journal.pone.0047891
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047891

2. Preliminary result of phase 2 study NCT01156909 at Haukeland University Hospital:
http://clinicaltrials.gov/ct2/show/NCT01156909
which is a continuation as a result of earlier postive result:
Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, et al. (2011) Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study. PLoS ONE 6(10): e26358. doi:10.1371/journal.pone.0026358
http://www.plosone.org/article/citationList.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0026358