No abstract

Two forms of linear DNAs have been found in simian (SFV1) and human (HSRV) spumaviruses: a linear duplex unsensitive to nuclease S1 and a sensitive structure with a single-stranded gap. Two nuclease S1 sensitive sites, mapping at the same position for both viruses, have been identified in the gapped structure. Using different molecular subgenomic clones of HSRV as probes in Southern blot analysis, one S1 site was localized in the 3'LTR and the other near the middle of the molecule at about 6.5 kbp from the 5' end of the viral genome. The latter site was shown to correspond to a single stranded region within the linear duplex DNA. Nucleotide sequence analysis revealed that the polypurine tract (PPT) usually found at the 5' boundary of the 3'LTR of retroviruses, is duplicated in HSRV at the 3' end of the pol gene, near the gap. This suggests that the synthesis of plus strand DNA is discontinuous, generating the gap.

Foamy viruses are a group of retroviruses of complex structure which were thought to be non‐pathogenic. The recent demonstration of neurological diseases in mice transgenic for human foamy virus (HFV) and the high prevalence of HFV sequences in Graves' disease question this idea. By PCR, we have detected HFV sequences with a non‐random deletion in the bel1 transactivator gene in other autoimmune conditions. Sequence analysis revealed that this deleted area corresponds to the excision of a known intron in bet, one of HFV's regulatory genes. The same phenomenon was observed in both acute and chronic infections, in vitro or in vivo, although the deleted forms were distinctly more abundant in chronic states. The viral DNA containing the bel1 deletion is apparently part of an otherwise complete genome, strongly suggesting that this provirus derives from the reverse transcription of a spliced pregenomic RNA. Bel1‐spliced provirus was shown to be defective when transfected into permissive cells. However, co‐expression with the Bel1 transactivator led to functional trans‐complementation and formation of viral particles. Splicing of the genome may be an important factor in HFV biology: genomes with the deletion may either interfere with wild‐type virus expression or alter host cell functions through background expression of viral regulatory proteins.

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

No abstract