Human spumaretrovirus-related sequences in the DNA of leukocytes from patients with Graves disease.

Abstract

Viruses, and more particularly retroviruses, have been postulated to play a role in the pathogenesis of autoimmune diseases. In a search for spumaretrovirus infection markers, we screened a group of 29 patients with Graves disease and a representative healthy population (23 subjects) as a control. Southern blot hybridization under s ent conditions, of patients' DNA extracted from peripheral blood lymphocyes, with a spumaretrovirus-specific genomic probe derived from the human spumaretroirus (HSRV) prototype, gave a positive signal in 10 cases. Moreover, by PCR, HSRVrelated sequences were detected in the DNA of 19 patients (66%). Positive DNA samples in Southern blots were also positive in PCR for all regions tested (gag, bell, li2, long terminal repeat). Amplified (gag and bel2) products were cloned and sequenced; they showed hih homology with HSRV. On the other hand, all 23 control subjects were negative by both procedures. Sera from both populations were ex for the presence of antibodies reactive with antigens of the spumaretrovirus family. These sera were negative by several immunodetection techniques: ELISA, indirect immunofluorescence, serum neutralization, and Western blotting. These results strongly suggest the existence of an assoclation between Graves disease and the presence of HSRV-related infection markers.Several clinical, genetic, and pathophysiological features support the notion of a role for autoimmunity in the pathogenesis of some endocrine conditions, such as Graves disease. In fact, the association of this affliction with other well-defined autoimmune nosological eptities-altered HLA expression, the. presence of autoantibodies, and modifications of certain lymphocyte subpopulations-favor this concept (1, 2).The possible involvement of different viruses in the etiology of autoimmune diseases has been evoked in animal models and in humans. Among viral agents, endogenous (3) and exogenous (4-6; §) retroviruses have been considered as likely candidates to be associated with this category of disorders. Animal models have produced evidence sustaining this hypothesis. For instance, in the genome of the obese chicken, which spontaneously develops autoimmune thyroiditis, an avian leukosis virus (ev22) has been identified (3). Moreover, type C retroviral particles have been detected in

Human foamy virus infection activates class I major histocompatibility complex antigen expression

“…However, by virtue of their genomic location and limited homology to certain human retrovirus regulatory genes, these proteins may have regulatory functions that qualitatively and quantitatively affect HFV gene expression as well as the expression of a number of important host cell genes or gene products such as cytokines or major histocompatibility complex (MHC) antigens. Recent results obtained in our laboratory suggest an association between spumaretrovirus molecular markers and Graves' disease (Lagaye et al, 1992). Alteration of human leukocyte antigen (HLA) expression may play a role in initiation of the autoimmune process, as previously described (Faustman et al, 1991;Roitt et al, 1992;Tolosa et al, 1992).…”

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

“…Additional isolates were reported later in patients with de Quervain thyroiditis (462) and dialysis encephalitis (85). Several attempts to determine the prevalence of HFV in different populations, both geographically and in relation to disease, particularly in thyroid disease and neurological disorders, have been made (6,64,85,268,363,462,525). However, those studies became controversial as different groups produced conflicting results (reviewed in reference 327).…”

“…HFV was linked to Graves' disease by serology, PCR, and Southern hybridization prior to the recognition that this virus is not a common human infection (268). In addition, sequences related to HIV-1 were detected in DNA from thyroid tissue and PBMCs of Graves' disease patients by Southern hybridization (100).…”

Detection and analysis of bovine foamy virus infection by an indicator cell line

“…Therefore, the method based on CPE may have a limitation on the titration of FV. Other methods, such as RT-PCR, which has been reported for the detection of prototype foamy viruses [11,12] , does not give the direct quantitation on viral loading during infection. Recently, a new method called the green fluorescent protein (GFP)-based indicator cell line was established for the titration of prototype foamy virus (PFV) and feline foamy virus (FeFV) [13,14] .…”