endogenous retrovirus and herpesvirus

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endogenous retrovirus and herpesvirus

Postby dignan » Tue Feb 12, 2008 9:09 am

More interesting evidence for multiple viruses / retroviruses at work in the MS disease process.

Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients.

Scand J Immunol. 2008 Mar;67(3):295-303.
Brudek T, Christensen T, Hansen HJ, Petersen T, Møller-Larsen A.
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. tb@microbiology.au.dk

Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays (ELISAs), we have performed a comparative study between MS patients and healthy controls to investigate the production of interferon (IFN)-gamma, interleukin (IL) 2, or IL-10 as well as the balance between Th1 and Th2 responses in supernatants from peripheral blood mononuclear cells (PBMC) stimulated with HERV and herpes antigen combinations. We have found a significant disproportion in Th1/Th2 responses in PBMCs from MS patients caused by the joint presence of HERV and herpes antigens. The results also showed a significantly higher IFN-gamma production in cells from MS patients; additionally, this production correlated with the synergistic cell proliferations whereas we did not find such a correlation in healthy controls. Our findings suggest that the increased production of IFN-gamma and the induced imbalance in Th1/Th2 responses favouring the inflammatory reactions in MS patients may lead to progression of the disease.

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Postby Lyon » Tue Feb 12, 2008 3:10 pm

Last edited by Lyon on Tue Nov 29, 2011 7:19 pm, edited 1 time in total.
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Postby rainer » Tue Feb 12, 2008 8:27 pm

Has anyone tried any of the herpes treatment (anti-virals) against MS? The relapse/remit similarity between the two seems like a pretty strong link.
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Postby dignan » Tue Feb 12, 2008 8:40 pm

I just saw this abstract from 2006 showing a significant correlation between a certain retrovirus and more active MS.

On a side note -- it was interesting looking in Pubmed at research on retroviruses and MS. I'm used to thinking there's some hot new topic in MS research, then going to Pubmed and finding studies on said topic going back to the 60s, 70s or, the latest, the 80s. A good reminder of how little I know. But with retroviruses, the research only went back to 1995. I find something about that encouraging. I think they're really on to something. I just hope it doesn't take them another 13 years to figure it out.

Multiple sclerosis-associated retrovirus in early multiple sclerosis: a six-year follow-up of a Sardinian cohort.

Mult Scler. 2006 Dec;12(6):698-703.
Sotgiu S, Arru G, Mameli G, Serra C, Pugliatti M, Rosati G, Dolei A.
Institute of Clinical Neurology, University of Sassari, Viale San Pietro 10, 07100, Sassari, Italy. stesot@hotmail.com

The human endogenous retroviruses (HERV)-W family contains an extracellular particle detected in multiple sclerosis (MS) patients and designated as MS-associated retrovirus (MSRV). Through nested RT-PCR assays specific for pol MSRV gene, we preliminary reported that its presence in the cerebrospinal fluid (CSF) of early MS patients could be indicative of a poor prognosis upon a three-year follow-up.

In the present clinical study, we enlarged our blind observation up to six years. At study entry, 10 MS patients were MSRV+ and eight were MSRV- in the CSF, both groups having a similar mean age and Expanded Disability Status Scale (EDSS) score. After six year follow-up, the mean EDSS significantly differed between the MSRV+ and MSRV- cohorts (4.3 versus 2.2; P = 0.004), as did the annual relapse rate (0.5 in the MSRV+ versus 0.3 in the MSRV-; P = 0.01). Finally, two MSRV+ patients entered the progressive phase, whilst none of the MSRV- group entered this phase, and 9/10 MSRV+ versus 2/8 MSRV patients were treated with immunomodulatory or immunosuppressive drugs (P = 0.009).

In conclusion, we found that the presence of MSRV virions in the CSF at the onset of MS is associated, not only with disability accumulation, but also with a higher rate of clinical re-exacerbations. With the known potential pathogenic effects of MSRV given in the literature, further investigations on MSRV are warranted.

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Postby CureOrBust » Wed Feb 13, 2008 5:09 am

rainer wrote:Has anyone tried any of the herpes treatment (anti-virals) against MS?
Which "ones" are they? I have tried Tamiflu and Amantadine (both being antivirals)
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Postby lyndacarol » Wed Feb 13, 2008 5:25 am

And I have tried acyclovir--Famvir--no effect.
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Postby dignan » Wed Feb 13, 2008 2:17 pm

Rainer, valacyclovir has been trialled for MS (see Pubmed abstract below) and didn't do too well. My understanding of the research on viruses and MS is that while still inconclusive, reactivation of the virus does not seem to drive actual relapses or progression immediately. Instead, viruses might somehow play more of a triggering role earlier in the process...but I'd wager that no researcher would be willing to make a definitive statement about the role of viruses in MS...

A randomized clinical trial of valacyclovir in multiple sclerosis.

Mult Scler. 2005 Jun;11(3):286-95.
Friedman JE, Zabriskie JB, Plank C, Ablashi D, Whitman J, Shahan B, Edgell R, Shieh M, Rapalino O, Zimmerman R, Sheng D.
Department of Neurology, New York University School of Medicine, NY, NY 10010, USA. jef4@med.nyu.edu

OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).

DESIGN/METHODS: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.

RESULTS: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.

CONCLUSIONS: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.
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