Three Sgp loci act independently as well as synergistically to elevate the expression of specific endogenous retroviruses implicated in murine lupus
| Autor: | Timothy J. Vyse, Kiyoaki Ito, Shozo Izui, Valérie Leroy, Leonard H. Evans, Masao Kihara, Lucie Clementine Baudino |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
viruses Immunology Congenic Endogenous retrovirus Locus (genetics) Antigen-Antibody Complex Biology Article Gene product Mice Mice Congenic 03 medical and health sciences 0302 clinical medicine Proviruses Viral Envelope Proteins Transcription (biology) hemic and lymphatic diseases Animals Immunology and Allergy Allele Glycoproteins 030304 developmental biology Genetics Mice Inbred BALB C 0303 health sciences Membrane Glycoproteins Endogenous Retroviruses TLR7 Provirus Lupus Nephritis Up-Regulation 3. Good health Cell biology carbohydrates (lipids) Toll-Like Receptor 7 RNA RNA Viral Molecular Chaperones 030215 immunology |
| Zdroj: | Journal of autoimmunity |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/j.jaut.2013.01.014 |
| Popis: | Endogenous retroviruses are implicated in murine lupus nephritis. They provide a source of nephritogenic retroviral gp70-anti-gp70 immune complexes through the production of serum gp70 protein and anti-gp70 autoantibodies as a result of the activation of TLR7. The Sgp (serum gp70 production) loci identified in lupus-prone mice play distinct roles for the expression of different classes of endogenous retroviruses, as Sgp3 regulates the transcription of xenotropic, polytropic and modified polytropic (mPT) viruses, and Sgp4 the transcription of only xenotropic viruses. In the present study, we extended these analyses to a third locus, Sgp5, using BALB/c mice congenic for the NZW-derived Sgp5 allele and also explored the possible interaction of Sgp3 and Sgp4 loci to promote the expression of endogenous retroviruses and serum gp70. The analysis of Sgp5 BALB/c congenic mice demonstrated that the Sgp5 locus enhanced the expression of xenotropic and mPT viruses, thereby upregulating the production of serum gp70. These data indicate a distinct action of the Sgp5 locus on the expression of endogenous retroviruses, as compared with two other Sgp loci. Moreover, comparative analysis of C57BL/6 double congenic mice for Sgp3 and Sgp4 loci with single congenic mice revealed that Sgp3 and Sgp4 acted synergistically to elevate the transcription of the potentially replication-competent Xmv18 provirus and the production of serum gp70. This indicates that the combined effect of three different Sgp loci markedly enhance the expression of endogenous retroviruses and their gene product, serum gp70, thereby contributing to the formation of nephritogenic gp70-anti-gp70 immune complexes in murine lupus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect