Is HERV activation a trigger for the development of MS? #MSBlog #MSResearch
"The following study provides in silico evidence that human endogenous retroviruses (HERVs) may play a role in MS and other associated autoimmune diseases. Specific HERV loci, or positions in our genomes, where these HERVs are integrated into our genome, are linked with MS, type 1 diabetes and rheumatoid arthritis (RA). Whether the linkage to these HERV loci are due to the HERVs or another gene, or regulatory element, in the genome close by is a moot point. However, there is other in vivo (within the body) and pathological evidence that HERVs are transcriptionally active in autoimmune diseases and the active HERV products may trigger the so called innate immune system to provide a danger signal that something is amiss in the nervous system, pancreas or joints. This danger signal may be what is required to trigger autoimmune cells to attack self and cause the disease-specific organ damage. This is why treatments that suppress HERV activation may work in these diseases and underpins our trial of raltegravir in MS. Interestingly, herpes viruses, in particular EBV, are known to transactivate HERVs and causes them to emerge from the genome. Therefore, drugs that block EBV activity may also suppress HERV activity. The so called dual viral hypothesis of MS is not a new concept and has been around for many years. I have discussed the EBV-HERV-MS link many times on this blog, therefore, for the regular readers there is noting new here."
"Who knows may be we will get an answer to viral and dual-viral hypotheses of MS in the next 10-20 years."
Background: Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian manner.
Objective: In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis.
Results: We found that at least one human endogenous retroviral locus was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis.
Conclusion: We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response.
CoI: I am the chief investigator of an investigator-led study testing the anti-HIV drug raltegravir in MS. This trial has been generously funded by Merck and sponsored by QMUL.