Dobrikova Elena, Florez Paola, Bradrick Shelton, Gromeier Matthias
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15125-30. doi: 10.1073/pnas.2436464100. Epub 2003 Nov 26.
We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3' non-translated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3' terminus that control IRES-mediated gene expression and virus propagation.
我们提出了一种基于脊髓灰质炎病毒嵌合体的癌症治疗方式，该嵌合体在源自2型人鼻病毒的内部核糖体进入位点（IRES）的翻译控制下进行复制。异源IRES的插入导致神经元特异性增殖缺陷，并消除了脊髓灰质炎病毒固有的神经毒性，而不影响源自恶性胶质瘤的细胞中的病毒生长。我们现在报告对由鼻病毒IRES介导的细胞类型特异性缺陷的分子机制的阐明。鼻病毒IRES在神经元细胞类型中的功能取决于病毒基因组3'非翻译区内的特定结构元件。我们的观察结果表明IRES与3'末端之间存在远程相互作用，可控制IRES介导的基因表达和病毒传播。
