Sgp3 and TLR7 stimulation differentially alter the expression profile of modified polytropic retroviruses implicated in murine systemic lupus.
Sgp3 and TLR7 stimulation differentially alter the expression profile of modified polytropic retroviruses implicated in murine systemic lupus.
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DOI：
10.1016/j.jaut.2012.03.002
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发表时间：
2012-06
影响因子：
12.8
通讯作者：
Izui S
中科院分区：
文献类型：
--
作者：
Leroy V;Kihara M;Baudino L;Brighouse G;Evans LH;Izui S
内源性逆转录病毒的包膜糖蛋白gp 70是与小鼠系统性红斑狼疮有关的主要致肾炎自身抗原之一。在不同的内源性逆转录病毒（亲嗜性，异嗜性和多变性），狼疮倾向的小鼠表达显着高水平的修饰的多变性（mPT）逆转录病毒，这是由Sgp 3（血清gp 70生产）基因座控制。为了确定来源于狼疮易感小鼠的Sgp 3基因座对特异性mPT前病毒表达的影响，通过克隆分析其转录本来确定在野生型和Sgp 3同源C57 BL/6小鼠的肝脏和胸腺中表达的不同mPT病毒的遗传来源。在C57 BL/6基因组中存在的13个mPT前病毒中，只有3个前病毒（Mpmv 6、Mpmv 10和Mpmv 13）在肝脏和胸腺中选择性但差异性地表达。这可能是与宿主基因共调控表达的结果，因为它们以相同的转录方向整合。与此相反，Sgp 3诱导的稳定状态表达的一个额外的选择组的mPT前病毒，并在TLR 7的刺激后，高度上调表达的一个潜在的复制能力的mPT病毒Mpmv 4。这些结果表明，不同亚群的mPT逆转录病毒的表达调节Sgp 3和TLR 7依赖的机制。潜在的复制能力的mPT病毒的诱导和一个这样的病毒在Sgp 3同源小鼠中用TLR 7刺激后的上调进一步强调了Sgp 3在通过TLR 7的活化针对致肾炎血清gp 70的自身免疫应答中的意义。
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 ontribution 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.
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遗传机制的解剖，涉及与鼠狼疮炎有关的血清逆转录病毒GP70的表达。
影响因子：
4.4
作者：
Baudino, Lucie;Yoshinobu, Kumiko;Morito, Naoki;Kikuchi, Shuichi;Fossati-Jimack, Liliane;Morley, Bernard J.;Vyse, Timothy J.;Hirose, Sachiko;Jorgensen, Trine N.;Tucker, Rebecca M.;Roark, Christina L.;Kotzin, Brian L.;Evans, Leonard H.;Izui, Shozo
通讯作者：
Izui, Shozo
影响因子：
4.8
作者：
Bulliard, Yannick;Wiznerowicz, Maciej;Trono, Didier
通讯作者：
Trono, Didier
影响因子：
5.4
作者：
Marin, M;Tailor, CS;Kabat, D
通讯作者：
Kabat, D
影响因子：
64.8
作者：
ELDER, JH;JENSEN, FC;LERNER, RA
通讯作者：
LERNER, RA
影响因子：
64.5
作者：
BARKLIS, E;MULLIGAN, RC;JAENISCH, R
通讯作者：
JAENISCH, R