Sgp3 and TLR7 stimulation differentially alter the expression profile of modified polytropic retroviruses implicated in murine systemic lupus
| Autor: | Leonard H. Evans, Masao Kihara, Valérie Leroy, Lucie Clementine Baudino, Shozo Izui, Guy Brighouse |
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| Rok vydání: | 2012 |
| Předmět: |
DNA Replication
Transcription Genetic viruses Immunology Congenic Endogenous retrovirus Thymus Gland Biology Article Virus Mice 03 medical and health sciences 0302 clinical medicine Proviruses Downregulation and upregulation medicine Animals Lupus Erythematosus Systemic Immunology and Allergy Gene Glycoproteins 030304 developmental biology Regulation of gene expression 0303 health sciences Genome Lupus erythematosus Mice Inbred NZB Adenine Endogenous Retroviruses TLR7 medicine.disease Virology Cell biology Mice Inbred C57BL Gene Expression Regulation Liver Toll-Like Receptor 7 Female Molecular Chaperones 030215 immunology |
| Zdroj: | Journal of autoimmunity |
| DOI: | 10.1016/j.jaut.2012.03.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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