Endogenous Retroviruses and Gene Regulation After Injury

广泛的分子和细胞类型与烧伤并发症的发展有关。 然而，烧伤后病理事件的复杂网络是如何被理解的仍然不是很清楚， 协调一致。内源性逆转录病毒（ERV）永久地整合到种系中，并且它们 分别占人类和小鼠基因组的~ 8%和~ 10%。我们最近的数据显示， 有证据表明，一组选择性的鼠ERVs（MuERVs）在小鼠的各种器官中被激活， 烧伤或败血症它们中的一些能够组装病毒颗粒和包膜糖蛋白 差异调节各种炎症介质和/或发挥细胞毒性作用。我们假设 烧伤引起的应激信号激活了某些ERV，随后是病毒体组装、感染， 随机重新整合到基因组中，导致免疫紊乱和对远处器官的损害。 具体目标。我们将评估抗逆转录病毒治疗对改善病理性 烧伤后小鼠免疫系统和其他远隔器官的变化。在这项研究中，我们将测试 通过抗逆转录病毒药物治疗抑制烧伤激活的MuERVs的假设改变了 烧伤后免疫系统和远隔器官的发病过程。靶向gag的siRNA MuERV的pol（组特异性抗原）、pol（逆转录酶）或env RNA以及抗逆转录病毒药物 将给予用于控制人类免疫缺陷病毒复制的药物 并将检查一组烧伤相关的病理生理标志物， 确定其功效。 这项研究的数据将为烧伤激活的MuERVs在烧伤后的病理作用提供直接的见解。 免疫系统紊乱和远处器官损伤。此外，这项研究的结果可能会导致 进一步研究开发一种新的烧伤患者治疗方案， 目前的方案。

A broad range of molecules and cell types have been implicated in the development of burn complications. However, it is still not clearly understood how the complex network of post-burn pathologic events is coordinated. Endogenous retroviruses (ERVs) are permanently incorporated into the germline and they constitute -8 % and -10 % of the human and mouse genomes, respectively. Our recent data provide evidence that a selective group of murine ERVs (MuERVs) are activated in various organs of mice after burn or sepsis. Some of them are able to assemble virus particles and the envelope (env) glycoproteins differentially modulate various inflammatory mediators and/or exert cytotoxic effects. We hypothesize that burn-elicited stress signals activate certain ERVs, followed by virion assembly, infection, and random reintegration into the genome resulting in immune disorder and damage to distant organs. Specific Aim. We will evaluate the effects of anti-retroviral treatment on the amelioration of pathologic changes in the immune system and other distant organs of mice after burn injury. In this study, we will test the hypothesis that inhibition of burn-activated MuERVs by treatment with anti-retroviral agents alters the course of post-burn pathogenesis in the immune system and distant organs. The siRNAs targeting gag (group specific antigen), pol (reverse transcriptase), or env RNA of the MuERVs as well as anti-retroviral agents prescribed for the control of replication of human immunodeficiency virus will be administered immediately after burn and a set of burn-associated pathophysiologic markers will be examined to determine their efficacy. The data from this study will provide direct insights into the pathologic roles of burn-activated MuERVs in immune disorder and damage to distant organs. Furthermore, the findings from this study may lead to a further investigation into the development of a novel therapeutic protocol for burn patients in combination with current regimens.