• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Functional profiling of a human cytomegalovirus genome
【24h】

Functional profiling of a human cytomegalovirus genome

机译：人类巨细胞病毒基因组的功能分析

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Human cytomegalovirus (HCMV), a ubiquitous herpesvirus, causes a lifelong subclinical infection in healthy adults but leads to significant morbidity and mortality in neonates and immunocompromised individuals. Its ability to grow in different cell types is responsible for HCMV-associated diseases, including mental retardation and retinitis, and vascular disorders. To globally assess viral gene function for replication in cells, we determined the genomic sequence of a bacterial artificial chromosome (EAC)-based clone of HCMV Towne strain and used this information to delete each of its 162 unique ORFs and generate a collection of viral mutants. The growth of these mutants in different cultured cells was examined to systematically investigate the necessity of each ORF for replication. Our results showed that 45 ORFs are essential for viral replication in fibroblasts and 117 are nonessential. Some genes were found to be required for viral replication in retinal pigment epithelial cells and microvascular endothelial cells, but not in fibroblasts, indicating their role as tropism factors. Interestingly, several viral mutants grew 10- to 500-fold better than the parental strain in different cell types, suggesting that the deleted ORFs encode replication temperance or repressing functions. Thus, HCMV encodes supportive and suppressive growth regulators for optimizing its replication in human fibroblasts, epithelial, and endothelial cells. Suppression of viral replication by virus-encoded temperance factors represents a novel mechanism for regulating the growth of an animal virus, and may contribute to HCMV's optimal infection of different tissues and successful proliferation among the human population.
机译：人类巨细胞病毒（HCMV）是一种普遍存在的疱疹病毒，在健康的成年人中会导致终生的亚临床感染，但会导致新生儿和免疫功能低下的人的严重发病率和死亡率。它在不同细胞类型中生长的能力与HCMV相关疾病有关，包括智力低下和视网膜炎以及血管疾病。为了全面评估病毒基因在细胞中复制的功能，我们确定了HCMV Towne菌株基于细菌人工染色体（EAC）的克隆的基因组序列，并使用此信息删除了其162个独特ORF中的每一个并生成了一系列病毒突变体。检查了这些突变体在不同培养细胞中的生长，以系统地研究每种ORF复制的必要性。我们的结果表明，45个ORF对成纤维细胞中的病毒复制至关重要，而117个则不是必需的。发现某些基因是视网膜色素上皮细胞和微血管内皮细胞中病毒复制所必需的，而成纤维细胞中则不是，这表明它们作为嗜性因子的作用。有趣的是，在不同的细胞类型中，几个病毒突变体的生长比亲本菌株好10到500倍，这表明缺失的ORF编码复制节制或抑制功能。因此，HCMV编码支持性和抑制性生长调节剂，以优化其在人成纤维细胞，上皮细胞和内皮细胞中的复制。通过病毒编码的节制因子抑制病毒复制代表了一种调节动物病毒生长的新机制，并且可能有助于HCMV对不同组织的最佳感染以及在人群中的成功增殖。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号