Virus within us!!!! Read on!!!

I happened to read a recent issue of the Science magazine DISCOVER and was drawn to an article about the discovery of an endogeneous retrovirus (enJSRV) found within the sheep's placenta that produces a viral protein that is crucial to the eventual birth of the foetus (Dunlap et al, 2006). It seems that inhibiting this viral protein will lead to the death of the foetus within 20 days. It has been speculated that this viral protein is more efficient than the native protein produced by the sheep that the former has replaced the latter's function during the birth process. The article concludes by saying that such an endogeneous virus will augment an immune response against the more lethal cousins of the endogeneous virus.

I thought the logic of everything was in place until the last part of the article, which states that the presence of the endogeneous virus helps to augment an immune response against the more lethal cousins of the endogeneous virus, which I find controversial and interesting. First and foremost, an immune response against a viral infection involves a whole repertoire of immune cells such as natural killer cells, B lymphocytes, CD4 T and CD8 T lymphocytes. Our immune system can develop tolerance for self proteins or proteins essential for life's functions, but it can also develop an immune response against foreign substances that can be potentially pathogenic. I thought that in the case of the pregnant sheep, the mother's body would have developed a tolerance against the endogeneous virus. An immune response, for instance the sequestration of viral proteins by antibodies, would not be beneficial, but harmful to the pregnant sheep, since inhibiting this viral protein would result in the foetus' death. The problem is that if the sheep encounters the more lethal cousins of the endogeneous virus, will the state of tolerance augment the immune response or render the sheep more susceptible?

This is an interesting topic considering the fact that remnants of viruses' genomes have persisted in our human genome in the form of retroviral transposons. Viral antigens are usually presented via the endogeneous pathway on MHC class I molecules. The question that remains is the potential involvement of these endogeneous viruses and retroviral transposons in the maturation of the immune cells, more specifically their role in the thymic education of T cells and B cells maturation in the bone marrow. It could also be that the exposure of the T cells to these resident viral antigens in the absence of co-stimuation leads to anergy. It has been shown that anergic T cells can act as suppressor T cells, which brings about tolerance (Lechler et al, 1999).

From a scientific perspective, it would be interesting as to how these endogeneous viruses and retroviral transposons interact with the immune system as it evolves, resulting in immune response or tolerance. Isn't it a coincidence that retroviruses have been the bane of Mankind? HIV, tumo-associated retroviruses, Hepatitis C, the list of wanted retroviral criminals goes on.....


Citations
1) Chai JG, Bartok I, Chandler P, Vendetti S, Antoniou A, Dyson J, Lechler R. Anergic T cells act as suppressor cells in vitro and in vivo. Eur J Immunol. 1999 Feb;29(2):686-92.

2) Dunlap KA, Palmarini M, Varela M, Burghardt RC, Hayashi K, Farmer JL, Spencer TE. Endogenous retroviruses regulate periimplantation placental growth and differentiation. Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14390-5.