Molecular and bioinformatic evidence of hepatitis C virus evolution in brain
Molecular and bioinformatic evidence of hepatitis C virus evolution in brain
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DOI：
10.1086/526519
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发表时间：
2008-02-15
影响因子：
6.4
通讯作者：
Branch, Andrea D.
中科院分区：
文献类型：
--
作者：
Fishman, Sarah L.;Murray, Jacinta M.;Branch, Andrea D.
背景丙型肝炎病毒（HCV）感染患者的神经认知功能障碍促使在脑中寻找HCV。通过5' UTR和E1（包膜1）基因分析，13例病毒血症患者中有7例（54%）脑内存在HCV。7例患者中有4例（57%）的脑HCV RNA共有序列与血浆和肝脏中的序列不同。从死后的大脑和肝脏的HCV RNA的质量进行了评估，并证明是适合的序列分析。准种分析显示，来自>1个脑区域的克隆中存在的几个突变在来自肝脏和血浆的克隆中不存在。大脑特异性突变定义了几个相关序列家族。这些家族中脑特异性突变的模式与HCV RNA从共同祖先的进化一致。单核苷酸多态性分析证实，一个突出的脑特异性突变构成了类似于10%的HCV RNA在小脑和髓质，但这种突变是在同一患者的肝脏和血浆中检测不到。这项研究介绍了新的方法来评估RNA从死后样本。它增加了大脑中HCV的报告病例，提供了来自大脑的第一个E1序列，并有助于越来越多的证据表明HCV在大脑中复制和进化。
Background. Neurocognitive deficits in patients with hepatitis C virus (HCV) infection prompted a search for HCV in brain.Results. HCV was present in the brains of 7 (54%) of 13 patients with viremia, as determined by 5' UTR and E1 (envelope 1) gene analysis. Brain HCV RNA consensus sequences differed from those in plasma and liver in 4 (57%) of 7 patients. The quality of HCV RNA from postmortem brain and liver was assessed and demonstrated to be suitable for sequence analysis. Quasispecies analysis revealed that several mutations present in clones from >1 brain region were absent in clones from liver and plasma. Brain-specific mutations defined several families of related sequences. The patterns of brain-specific mutations in these families were consistent with the evolution of HCV RNA from a common ancestor. Single-nucleotide-polymorphism analysis confirmed that a prominent brain-specific mutation constituted similar to 10% of HCV RNA in cerebellum and medulla but that this mutation was undetectable in the liver and plasma of the same patient.Conclusions. This study introduces novel methods for assessing RNA from postmortem samples. It increases the reported cases of HCV in the brain, provides the first E1 sequences from the brain, and contributes to the growing evidence that HCV replicates and evolves within the brain.