Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders
Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders
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DOI：
10.1128/jvi.79.17.10890-10901.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Seifarth, W
中科院分区：
文献类型：
--
作者：
Frank, O;Giehl, M;Seifarth, W
在新近发作的精神分裂症和情感性精神障碍患者的脑样本、脑脊液和血浆中检测和鉴定逆转录病毒转录本表明，不同的人类内源性逆转录病毒（HERVs）的激活或上调可能在神经精神疾病的发病机制中发挥作用。为了验证这一假设，我们对人脑中HERV的转录活性进行了全面的基于微阵列的分析。我们调查了20个HERV家族的50个代表性成员，共215个脑样本，来自精神分裂症或双相情感障碍患者和匹配的对照组。发现特征性脑特异性逆转录病毒活性谱由I类家族HERV-E、HERV-F和ERV 9的成员和HERV-K分类群的成员组成。除了这些组成型表达的HERV外，在所有脑样品中鉴定了许多差异活性HERV元件，这些元件与疾病模式无关，可能反映了受试个体遗传背景的差异。与健康大脑相比，HML-2家族的一个亚组（HERV-K10）在双相情感障碍和精神分裂症相关样本中的代表性显著过高，表明与疾病存在潜在关联。实时PCR分析HERV env转录物的编码能力可能涉及神经炎症条件显示，无论临床表现如何，HERV-W，HERV-FRD和HML-2的env表达均不受影响。我们的数据表明，HERV在大脑中的转录与精神分裂症和相关疾病的相关性很弱，但可能受到个体遗传背景，脑浸润免疫细胞或药物治疗的影响。
The detection and identification of retroviral transcripts in brain samples, cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia and schizoaffective disorders suggest that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive microarray-based analysis of HERV transcriptional activity in human brains. We investigated 50 representative members of 20 HERV families in a total of 215 brain samples derived from individuals with schizophrenia or bipolar disorders and matched controls. A characteristic brain-specific retroviral activity profile was found that consists of members of the class I families HERV-E, HERV-F, and ERV9 and members of HERV-K taxa. In addition to these constitutively expressed HERVs, a number of differentially active HERV elements were identified in all brain samples independent of the disease pattern that may reflect differences in the genetic background of the tested individuals. Only a subgroup of the HML-2 family (HERV-K10) was significantly overrepresented in both bipolar-disorder- and schizophrenia-associated samples compared to healthy brains, suggesting a potential association with disease. Real-time PCR analysis of HERV env transcripts with coding capacity potentially involved in neuroinflammatory conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains unaffected regardless of the clinical picture. Our data suggest that HERV transcription in brains is weakly correlated with schizophrenia and related diseases but may be influenced by the individual genetic background, brain-infiltrating immune cells, or medical treatment.