Human Endogenous Retroviruses (HERVs) can participate in numerous diseases, especially autoimmune, (neuro)degenerative, cancers, etc.
ERVs have been around for a very long time and have altered immune responses in many species including in humans (see the link). Depending upon the type of ERVs, their numbers in the human genome, and the regulatory sequence they harbor, it is likely that these ERVs in humans contribute to the number of outcomes, including those you mentioned.
Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=endogenous+retrovirus%2C+aim2
There is very interesting story about MMTV (mouse mammary tumor virus) in mice. Normally, this retrovirus encodes superantigen, necessary for stimulation of proliferation of T lymphocytes, which the virus uses for amplification. Superantigens (SAGs) represented in different viral isolates show specificity to corresponding V beta segments of TCRs. Then, the virus uses corresponding T cells to reach mammary gland epithelium as target tissue and further infect offspring. Endogenous MMTVs are well described in different mouse strains as MLS antigens, (mixed lymphocyte stimulation) because they encode proteins capable to induce mixed lymphocyte reaction in vitro, even if responding and stimulating lymphocytes share the same MHC antigens. Expression of these ERVs in vivo, in mouse thymus, results in deletion of clones with corresponding Vbetas and their absence in periphery. This makes impossible viral life cycle and prevents induction of mammary cancers. This story is well represented in works by Tatyana Golovkina and co-authors. This rises very intriguing question, how much this story has relation to human mammary cancers.
Despite the fact that HERVs are known to be present as remnants of viral infection in a significant proportion of our genomic DNA, there is no convincing evidence to date linking their presence, and their potential expression, as a mechanism for breaking immune tolerance and triggering human autoimmune diseases. Yes, evidences of the presence of HERVs have been reported in systemic lupus erythematous, rheumatoid arthritis and Sjogren´s syndrome, yet no animal model or striking data in human diseases have been produced as irrefutable proof of their direct role in the pathogenesis of autoimmune diseases.
Dr Boban,
I have no specific opinion except to acknowledge that HERVs exist and to agree with the three previous correspondents. Indeed, their very existence generated many hypotheses in the etiopathogeny of many diseases where a chronic immuno-inflammatory dysfunction is present. More than 25 years ago, I reviewed a grant dealing with HERVs and autoimmune diseases (RA and SLE). Very exciting prospects but highly circumstantial arguments, then. I nevertheless gave a favourable rating hoping the researchers would obtain hard data and beef up the speculative basis of their application. I am still following their (lack of) progress via PUBMED but, still hoping. If one was to start a research career on this topic, one would have to look at a very long term enterprise with slow incremental progress. I would advise to concommittantly have an easier research plan B to fall back on.
Best
HA Ménard, MD FRCP(C), Emeritus Professor of Medicine, McGill U.
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