Age- and disease-dependent HERV-W envelope allelic variation in brain: association with neuroimmune gene expression.

Age- and disease-dependent HERV-W envelope allelic variation in brain: association with neuroimmune gene expression.
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DOI:
10.1371/journal.pone.0019176
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发表时间:
2011-04-29
期刊:
影响因子:
3.7
通讯作者:
Power C
Power C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bhat RK;Ellestad KK;Wheatley BM;Warren R;Holt RA;Power C

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糖蛋白 Syncytin-1 由人内源性逆转录病毒 (HERV)-W env 基因编码,能够诱导神经炎症。负责大脑中 Syncytin-1 表达的特定等位基因尚不确定。在此,使用多平台方法在神经系统中检查了 HERV-W env 多样性以及 Syncytin-1 丰度和宿主免疫基因谱。与星形胶质细胞和小胶质细胞中较少的染色体多样性相比,HERV-W env 序列由原代人类神经元中的多个染色体编码位点编码(p<0.05)。从全身或神经系统疾病患者大脑中克隆的 HERV-W env RNA 序列主要源自染色体位点 7q21.2。在同一样本中,HERV-W env 转录物水平与多种促炎基因的表达相关(p<0.05)。大脑转录组的深度测序揭示了 env 转录本是最丰富的 HERV-W 转录本,与健康成人大脑标本相比,在胎儿中表现出更高的表达。 Syncytin-1 在健康大脑样本中的表达源自多个编码位点,并与不同的免疫和发育基因谱相关。疾病期间大脑中 Syncytin-1 的表达与神经炎症相关,并且主要由全长原病毒编码。目前的研究还强调了大脑内 HERV 基因表达的多样性,并强化了 HERV 表达对神经炎症疾病的潜在贡献。
The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W env gene and is capable of inducing neuroinflammation. The specific allele(s) responsible for Syncytin-1 expression in the brain is uncertain. Herein, HERV-W env diversity together with Syncytin-1 abundance and host immune gene profiles were examined in the nervous system using a multiplatform approach. HERV-W env sequences were encoded by multiple chromosomal encoding loci in primary human neurons compared with less chromosomal diversity in astrocytes and microglia (p<0.05). HERV-W env RNA sequences cloned from brains of patients with systemic or neurologic diseases were principally derived from chromosomal locus 7q21.2. Within the same specimens, HERV-W env transcript levels were correlated with the expression of multiple proinflammatory genes (p<0.05). Deep sequencing of brain transcriptomes disclosed the env transcripts to be the most abundant HERV-W transcripts, showing greater expression in fetal compared with healthy adult brain specimens. Syncytin-1's expression in healthy brain specimens was derived from multiple encoding loci and linked to distinct immune and developmental gene profiles. Syncytin-1 expression in the brain during disease was associated with neuroinflammation and was principally encoded by a full length provirus. The present studies also highlighted the diversity in HERV gene expression within the brain and reinforce the potential contributions of HERV expression to neuroinflammatory diseases.
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