Wednesday, 2 November 2011

Research: HERVs and susceptibility to MS



Background: It has been suggested that the occurrence of multiple sclerosis (MS) may be associated with human endogenous retroviruses (HERV; a virus that has integrated into the genome), specifically the X-linked (female chromosome) viral locus HERV-Fc1.


The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients are generally subdivided into Remitting/Relapsing and Secondary Progressive and Primary Progressive.


Results: In this study of 1181 MS patients and 1886 controls we found that relapsing remitting and secondary progressive MS were associated with the C-allele of the marker rs391745 near the HERV-Fc1 locus (p = 0.003), while primary progressive disease was not.




Conclusions: The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS.


For a cell to divide needs the genetic code to be replicated. This requires DNA to divide. When protein is made from the code of DNA it is translated into RNA and this codes the amino acids. Viruses reproduce themselves by hi-jacking the machinery of the cell to reproduce itself. Some virus particles have DNA but others have RNA that has to be reversed engineered (Retro means going back) to produce viral DNA so that it can make new infective particles. A retrovirus refers to a virus that has viral RNA. The Human Immunodeficiency Virus that causes Acquired Immunodeficiency disease is an example of a retro virus. This is a an exogenous retrovirus because if comes form outside of the body to infect the cell. However in our history some of these viruses have intregrated into our DNA and they become endogenous retrovirus (ERV). There are a number of Human ERV present in the body and if is not clear what they do. In the Mouse there are a number of ERV that shape the immune repetoire (i.e. defines the surival or death of some types of white blood cells, which then impacts on what the immmune system can respond to.


When genetists state that the presence of a gene is actually involved in the disease process they are looking for evidence that the gene and the genes are causally linked. In this study they found that HERV-F1 occurs more commonly in relapsing MSers than PP MSers . In this particulalr study the likehood of the results occuring by chance when there is no association with the development of MS and the presence of HERV in the genome is three in a thousand experiments (P=0.003). So it was considered unlikely that the result occurred by chance and suggested that the presence of HERV was associated with RR MS.

However for genetists to be accept that there is something in the observation they would want the chance of the event occuring to be less than one in a thousand observations if it were not related (this criteria is not met in this study). The main gene cluster that has been linked to susceptibility of MS is called the MHC and this oberservation would now only occur by chance in about 1 in a trillion, trillion, trillion, trillion, trillion, trillion, trillion, trillion, trillion, trillion times if it were not liked to disease. So I think we can say that a variant of the MHC is linked to susceptibility ofMS.

Sometimes these ERV remain inactive, but sometimes particularly during cell division, it is possible that that these sleeping HERV (human ERV) can become reactivated and there is some evidence that HERV viral particals can be found more commonly in the blood at the time of relapses. Is this causal or a consquence of this the disease activity is unknown. Could this interact with reponses and activity of Epstein Bar virus that influence disease, we don't knowBut one way to look at this is to try and treat with anti-retrovial agents and see what happens.

4 comments:

  1. Alright mouse,

    can you try to rephrase in layman wording?
    We got used to the fonts in Italic at the bottom of each post being more "reader-friendly".
    You seem to be swimming against the tide on this last one.

    ReplyDelete
  2. OK I see your point,sorry............
    shoot the boss for not sub-editing the language before posting.

    ReplyDelete
  3. It seemed to make sense when I wrote comment it, but in the light of day...your right.....it's garbage. I have asked retrovirus bod to comment. Then I will explain what I was trying to say. Until then I've deleted my babble.

    ReplyDelete
  4. Hope this makes more sense. The retro virus bod was too slow so I have cobbled something together

    ReplyDelete

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