[Endogenous retroviral sequences as a factor in the pathogenesis of systemic lupus erythematosus].
Endogenous retroviral sequences (ERV) are integrated parts of the human genome. They make up at least 1% of the total genomic DNA. This pool of genetic material might help explain the long discussed role of retroviruses in autoimmune disease. Their proviral features suggest two possible models leading to autoimmune disease: the mobile insertion into a or near a somatic gene, changing its function, and the expression of proteins by ERV, which then might act as autoantigens or superantigens. These mechanisms are supported by prior studies of systemic lupus erythematosus (SLE). In MRL-lpr/lpr mice with SLE-like disease the insertion of a mobile retroviral element, the early transposon (ETn), into the second intron of the fas gene leads to reduced apoptosis, accumulation of lymphocytes and earlier mortality. Investigations of murine and human SLE demonstrate autoantibodies against self-proteins, which crossreact with retroviral proteins. Future investigations may further establish the interrelation between the activation of endogenous retroviral sequences and SLE with its multifactorial genetic determinants.
Walchner
M
M
Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München.
Leib-Mösch
C
C
Messer
G
G
Kind
P
P
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D004251:DNA Transposable Elements / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics*; D016678:Genome; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000821:virology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D016662:Virus Integration / Q000235:genetics*
D004251:DNA Transposable Elements; D004279:DNA, Viral