Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins.
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins.
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DOI：
10.1186/s13024-018-0275-3
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发表时间：
2018-08-02
影响因子：
15.1
通讯作者：
Goodier JL
中科院分区：
文献类型：
--
作者：
Mayer J;Harz C;Sanchez L;Pereira GC;Maldener E;Heras SR;Ostrow LW;Ravits J;Batra R;Meese E;García-Pérez JL;Goodier JL
肌萎缩侧索硬化症(ALS)是一种致命的神经退行性疾病。大约90%的肌萎缩侧索硬化症病例没有已知的遗传原因。最近有报道称，人内源性逆转录病毒多拷贝HERV-K(HML-2)组由于转录上调和HML-2包膜蛋白(Env)的毒性作用，可能与ALS的神经退行性变和疾病发病有关。Env和其他蛋白质是由一些转录活性HML-2基因座编码的。然而，需要更详细的信息，关于ALS中哪些HML-2基因座被转录，它们的哪些蛋白被表达，以及疾病和非疾病状态之间的差异。对于ALS患者和对照组的脑和脊髓组织样本，我们通过生成和定位HML-2特异的cDNA序列来鉴定转录的HML-2基因座。根据观察到的cDNA序列，我们预测了HML-2 env基因衍生蛋白的表达。此外，我们通过RT-qPCR检测了HML-2的转录水平，并通过Western blotting检测了ALS和对照组织中HML-2 Env蛋白的存在。我们鉴定了24个不同转录水平的HML-2基因座。其中一些基因座的转录水平相对较高。然而，当比较ALS和对照组时，没有发现HML-2基因座转录活性的显著差异。同样，通过RT-qPCR检测，ALS和对照组之间的总体HML-2转录水平没有显著差异。事实上，我们无法在肌萎缩侧索硬化症和对照组织样本中检测到全长HML-2 Env蛋白，尽管有合理的敏感性。相反，我们的分析表明，除全长Env外，许多HML-2蛋白变体可能在ALS患者中表达。我们的结果扩展和提炼了最近关于HERV-K(HML-2)和ALS的出版物。我们的一些结果与最近的发现相矛盾，需要进一步的具体分析。我们对ALS中HML-2转录的分析打开了这样一种可能性，即在研究HML-2在ALS疾病中的作用时，可能必须考虑典型的全长Env以外的HML-2蛋白。本文的在线版本(10.1186/s130240180275-3)包含补充材料，可供授权用户使用。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease. The online version of this article (10.1186/s13024-018-0275-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.7
作者：
Agoni L;Guha C;Lenz J
通讯作者：
Lenz J
影响因子：
5.2
作者：
Douville RN;Nath A
通讯作者：
Nath A
影响因子：
3.3
作者：
Fuchs NV;Loewer S;Daley GQ;Izsvák Z;Löwer J;Löwer R
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Löwer R
影响因子：
8
作者：
Boese, A;Sauter, M;Mueller-Lantzsch, N
通讯作者：
Mueller-Lantzsch, N
影响因子：
11.2
作者：
Douville, Renee;Liu, Jiankai;Rothstein, Jeffrey;Nath, Avindra
通讯作者：
Nath, Avindra