title: Sgp3 and TLR7 stimulation differentially alter the expression profile of modified polytropic retroviruses implicated in murine systemic lupus.
abstract: The envelope glycoprotein, gp70, of endogenous retroviruses represents one of the major nephritogenic autoantigens implicated in murine systemic lupus erythematosus. Among different endogenous retroviruses (ecotropic, xenotropic and polytropic), lupus-prone mice express remarkably high levels of modified polytropic (mPT) retroviruses, which are controlled by the Sgp3 (serum gp70 production) locus. To define the contribution of the Sgp3 locus derived from lupus-prone mice to the expression of the specific mPT proviruses, the genetic origin of different mPT viruses expressed in livers and thymi of wild-type and Sgp3 congenic C57BL/6 mice was determined through clonal analysis of their transcripts. Among 13 mPT proviruses present in the C57BL/6 genome, only 3 proviruses (Mpmv6, Mpmv10 and Mpmv13) were selectively but differentially expressed in livers and thymi. This was likely a result of co-regulated expression with host genes because of their integration in the same transcriptional direction. In contrast, Sgp3 induced the steady-state expression of an additional select group of mPT proviruses and, after stimulation of TLR7, the highly upregulated expression of a potentially replication-competent mPT virus Mpmv4. These results indicated that the expression of distinct subpopulations of mPT retroviruses was regulated by Sgp3- and TLR7-dependent mechanisms. The induction of potentially replication-competent mPT viruses and the upregulation of one such virus after stimulation with TLR7 in Sgp3 congenic mice further highlight the implication of Sgp3 in autoimmune responses against nephritogenic serum gp70 through the activation of TLR7.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Leroy
authors.forename: Masao
authors.initials: M
authors.lastname: Kihara
authors.forename: Lucie
authors.initials: L
authors.lastname: Baudino
authors.forename: Guy
authors.initials: G
authors.lastname: Brighouse
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Evans
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004261:DNA Replication; D020077:Endogenous Retroviruses / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016678:Genome; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011533:Proviruses / Q000235:genetics; D013950:Thymus Gland / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D006023:Glycoproteins; D018832:Molecular Chaperones; C508876:SM360320; C479954:Sgp3 protein, mouse; D051199:Toll-Like Receptor 7; D000225:Adenine