Perspectives on the Role of Endogenous Human Retroviruses in Autoimmune Diseases

• Published in: Virology 2002-04, Vol.296 (1), p.1-5
• Main Author: Portis, John L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Viral - blood; Autoimmune Diseases - blood; Autoimmune Diseases - virology; Endogenous Retroviruses - genetics; Endogenous Retroviruses - immunology; Endogenous Retroviruses - physiology; Gene Expression; Humans; Superantigens - immunology; T-Lymphocytes - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2002.1388

The concept that a persistent viral infection can be associated with untoward consequences temporally remote from the initial infection is now a familiar one. Examples include the immunodeficiency caused by HIV, spastic paraparesis associated with HTLV-1, chronic hepatitis and the attendant progressive cirrhoses associated with HBV and HCV, and the neurological diseases SSPE, and PML associated with persistence of measles and polyomavirus, respectively. The agents which cause these diseases are all of exogenous origin and the respective tissue pathologies are either a consequence of direct cytopathic effects of the virus infection or secondary to inflammatory responses it engenders. Generally signs of persistent viral gene expression can be detected throughout the course of disease. There is abundant evidence from animal models that viruses can also cause chronic diseases by inducing autoimmunity. Viral antigens can structurally mimic self-antigens and initiate an immune response which cross-reacts with the respective autoantigens (molecular mimicry). This then sets the stage for a local inflammatory response near the site of autoantigen expression, which in turn leads to tissue damage. Viruses need not necessarily persist. Once started, the autoreactive process can be self-sustaining through epitope spreading. Much of what we know about these mechanisms has come primarily from studies in animal models, but there is compelling epidemiologic evidence that virus infection in humans predisposes one to autoimmune diseases. The reader is referred to a recent review on the subject. It has become apparent that essentially all eukaryotes including man contain an abundance of endogenous retroviral genomes archived within their genomic DNA. The potential capacity of these elements to move about the genome, modifying host genes or their expression programs, and the ability of some retroviral proteins to modulate immune responses, has suggested that these prototypical persistent viruses might also have a hand in autoimmune diseases. Following is a discussion of the nature of the evidence and the placement of some of these observations in a historical perspective drawn from animal studies.