human endogenous retrovirus

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human endogenous retrovirus

Postby dignan » Thu Nov 23, 2006 8:08 am

human endogenous retrovirus seems to be another virus to add to the list of suspects along with EBV and HHV6.



Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway.

J Neuroimmunol. 2006 Nov 15;
Christensen T, Petersen T, Thiel S, Brudek T, Ellermann-Eriksen S, Moller-Larsen A.
Institute of Medical Microbiology and Immunology, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.

Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3.

For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env and disease activity was demonstrated, as were indications of a protective effect of high MBL and MASP-3 levels. The HLA alleles B()07, DRB()02, and DQB1()06 were commonly present together in the MS families, both in MS patients, and in unaffected family members.

Our results support that HERV-H and the antiviral immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
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Postby BioDocFL » Fri Nov 24, 2006 9:52 am

I like the topics popping up recently on ThisIsMS: “epigenetics” and “retroviruses”.

If there is retroviral activity going on in a cell, that means active reverse transcriptase activity. An interesting article (Dewannieux M., Esnault C. & Heidmann T. ‘LINE-mediated retrotransposition of marked Alu sequences’ Nature Genetics (2003) 35:41-48 ) demonstrates that Alu sequences could be picked up preferentially by reverse transcriptases and retrotransposed due to the association of Alu RNA transcripts with the ribosome. What does this mean? Think ‘epigenetic control’.
If Alu sequences are retrotransposed, that means the creation of many Alu DNA sequences of about 80-410 bases in length. There are an estimated 500,000 Alu genes in the human genome so there could be lots of Alu RNA around in a cell. (Look at Li & Steinman, Arthritis Rheum 1989 32:726-33, relates to GC and Alu content in free DNA in serum in lupus. I am convinced lupus and MS are related so I read about both.) Alu sequences are very rich in GC content. The cytosines should be methylated, otherwise the DNA will be hypomethylated and appear to be foreign DNA and could provoke a reaction from the immune system. Because these Alu DNAs are so rich in GC, they would require a lot of the cell’s S-adenosylmethionine (SAM). SAM is needed for the methylation of DNA and histones, which is a major aspect of epigenetic control. Epigenetic control is what keeps genes from being over-expressed. If a cell suddenly has trouble establishing and maintaining its epigenetic control patterns on genes, the wrong genes could potentially become active. In immature cells that are actively replicating, that could lead to cancer. In more mature cells, it could mean an imbalance in some function that is occasionally switched off and on, like heat-shock response as an example, or it could lead to apoptosis in the cell. In MS the hypomethylated Alu DNA might not become a direct auto-antigen due to difficulty in it crossing the blood brain barrier but the disruption of epigenetic control could result in problems synthesizing myelin. Whereas in lupus the hypomethylated Alu DNA could get into the blood easily and become an auto-antigen because it can be seen by the immune system. In lupus the disruption of epigenetic control in connective tissue cells could result in problems synthesizing collagen.
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LUPUS/MS relationship

Postby Lyon » Fri Nov 24, 2006 10:25 am

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Last edited by Lyon on Mon Jun 20, 2011 1:51 pm, edited 1 time in total.
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Postby BioDocFL » Fri Nov 24, 2006 11:43 am

I should probably do an indepth comparison sometime but, for a start, just some of the similarities:

1. Female predominance is about 90% in lupus, about 60-70% in MS. I've
seen different numbers but typically this is about what you see.
2. Onset is usually in early adulthood.
3. Both lupus and MS are considered to be multiple gene diseases.
4. Both have had possible retroviral aspects mentioned in the literature.
5. Both have some heritable aspects, and families can be found that have occurence of MS, lupus, and RA in them above the general population.
6. I think there can be co-occurence of MS and lupus in some patients and that may be greater than the odds in the general population for a person to get either of them. (I'm not completely sure of this, I need to research it and find references, so let's leave it as only a possibility.)
7. Some of the other possible causes are mentioned for both such as toxins (heavy metals in MS, hair dyes in lupus), or viruses.
8. CNS problems can occur in both.
9. Lupus is known for light-sensitivity but I think in MS there is some mention of this, perhaps more so related to heat than the UV light.
10. MS patients can sometimes get skin lesions, which is a hallmark of lupus. I think hair loss can occur in both also.
11. Sjogren's syndrome can appear in both and in arthritis patients.
12. Possible involvement of the X chromosome: There are chromosomal abnormalities seen in MS (D’Alessandro E., Cola M. D., Re M. L. L., et al. Nonrandom chromosome changes in multiple sclerosis. Am J Med Genet 1990; 37: 406-411. ) many of which are related to the X chromosome according to those authors. In lupus, there is a case of lupus in an XX male who had only a small section of a Y chromosome, which just happened to be inserted into the end of the X chromosome's short arm. (Chagnon, et al. 'Identification and characterization of an Xp22.33;Yp11.2 translocation causing a triplication of several genes of the pseudoautosomal region 1 in an XX male patient with severe systemic lupus erythematosus' Arthritis Rheum 2006;54:1270-78. ) Some patient and carriers of another disease, X-linked chronic granulomatous disease, which is associated with this area of the X chromosome sometimes have lupus symptoms.
13. The difficulties in diagnosing MS, while eliminating other possibilities may in fact be because of it having the same cellular mechanism going on, just different cell types and therefore symptoms appearing.
14. We mentioned in another topic a long time ago the analysis of gene expression patterns between lupus, MS, and normal subjects. There were some similarities between the lupus and MS patients. Those similarities could be due to a similar mechanism, the differences could be due to the reaction to the mechanism based on the different cell types and tissue location initially involved and the accessibility of auto-antigens (inside the blood-brain barrier vs. outside).

Also, think of how the differences could be explained. For example, one of the biggest problems in lupus is circulating auto-antibodies/auto-antigen complexes which can deposit or possibly originate in the kidneys. This then creates the problems of malfunctioning kidneys, a secondary event that becomes a major concern. In MS, most of the auto-antigens are inside the blood-brain barrier so there is little kidney involvement due to circulating complexes. In MS there could be failure in some location of the brain that then affects a nerve bundle going to an organ (vision problems for example). In both these cases, (circulating auto-antigens or vision problems) the initial event occurred in one cell type (chondrocytes generating auto-antigens in lupus, oligodendrocytes not making enough myelin in MS) but then affected another organ.

I could probably think of more. Maybe I will try to do a more detailed comparison and send it somewhere for publishing.

Wesley
Last edited by BioDocFL on Fri Nov 24, 2006 12:23 pm, edited 1 time in total.
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