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Title

Selective up-regulation of intact, but not defective env RNAs of endogenous modified polytropic retrovirus by the Sgp3 locus of lupus-prone mice

Authors
Yoshinobu, Kumiko
Morley, Bernard J.
Evans, Leonard H.
Published in Journal of Immunology. 2009, vol. 182, no. 12, p. 8094-103
Abstract Endogenous retroviruses are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Because four different classes of endogenous retroviruses, i.e., ecotropic, xenotropic, polytropic, or modified polytropic (mPT), are expressed in mice, we investigated the possibility that a particular class of endogenous retroviruses is associated with the development of murine SLE. We observed >15-fold increased expression of mPT env (envelope) RNA in livers of all four lupus-prone mice, as compared with those of nine nonautoimmune strains of mice. This was not the case for the three other classes of retroviruses. Furthermore, we found that in addition to intact mPT transcripts, many strains of mice expressed two defective mPT env transcripts which carry a deletion in the env sequence of the 3' portion of the gp70 surface protein and the 5' portion of the p15E transmembrane protein, respectively. Remarkably, in contrast to nonautoimmune strains of mice, all four lupus-prone mice expressed abundant levels of intact mPT env transcripts, but only low or nondetectable levels of the mutant env transcripts. The Sgp3 (serum gp70 production 3) locus derived from lupus-prone mice was responsible for the selective up-regulation of the intact mPT env RNA. Finally, we observed that single-stranded RNA-specific TLR7 played a critical role in the production of anti-gp70 autoantibodies. These data suggest that lupus-prone mice may possess a unique genetic mechanism responsible for the expression of mPT retroviruses, which could act as a triggering factor through activating TLR7 for the development of autoimmune responses in mice predisposed to SLE.
Keywords AllelesAmino Acid SequenceAnimalsBase SequenceEndogenous Retroviruses/genetics/metabolismGene Products, env/genetics/metabolismGlycoproteins/genetics/metabolismLupus Erythematosus, Systemic/metabolismMembrane Glycoproteins/metabolismMiceMolecular Chaperones/genetics/metabolismMolecular Sequence DataMutation/geneticsRNA, Viral/geneticsSequence AlignmentToll-Like Receptor 7/metabolismTranscription, Genetic/geneticsUp-Regulation
Identifiers
PMID: 19494335
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Structures
Research groups Lupus érythémateux systémique, de l'anémie hémolytique et de la glomérulonéphrite (168)
Groupe Reith Walter (pathologie et immunologie) (282)
Groupe Santiago-Raber Marie-Laure (pathologie et immunologie) (915)
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(ISO format)
YOSHINOBU, Kumiko et al. Selective up-regulation of intact, but not defective env RNAs of endogenous modified polytropic retrovirus by the Sgp3 locus of lupus-prone mice. In: Journal of Immunology, 2009, vol. 182, n° 12, p. 8094-103. https://archive-ouverte.unige.ch/unige:5579

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Deposited on : 2010-03-25

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