German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Int J Oncol. 2012 Jan;40(1):287-98. doi: 10.3892/ijo.2011.1222. Epub 2011 Oct 4.
Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic properties which shows promising effects in the treatment of cancer. Anti-cancer effects are due to the virus ability: i) to replicate in and kill tumor cells, leading finally to their selective elimination; and ii) to induce the stimulation of antitumor activities in immune cells. NDV does not harm normal cells and has a high safety profile. In this study, we first report a direct correlation between the degree of cell resistance to NDV infection and the cellular expression of the retinoic acid-inducible gene I (RIG-I) which is a cytosolic viral RNA receptor. RIG-I plays an important role in the recognition of and response to infection by RNA viruses. We also demonstrate that impairment of the interferon (IFN) pathway through deletion of the receptor for type I IFN (IFNR1) in primary macrophages leads to NDV replication. In tumor cells, addition of exogenous IFN-α4 is shown to lead to tumor growth reduction and inhibition of viral replication. Finally, increase of the RIG-I concentration of tumor cells via plasmid transfection is shown to be associated with a stronger resistance to NDV infection. These findings shed new light on the crucial role played by the cytosolic receptor RIG-I and the plasma membrane receptor IFNR1 as key molecules to protect cells against infection by NDV.
新城疫病毒（NDV）是一种具有溶瘤特性的禽副粘病毒，在癌症治疗中显示出有前景的效果。抗癌作用是由于该病毒具有以下能力：i）在肿瘤细胞中复制并杀死肿瘤细胞，最终导致其选择性消除；ii）诱导免疫细胞中抗肿瘤活性的刺激。NDV 不会伤害正常细胞，具有很高的安全性。在这项研究中，我们首先报告了细胞对 NDV 感染的抵抗力与细胞表达视黄酸诱导基因 I（RIG-I）之间的直接相关性，RIG-I 是一种细胞溶质病毒 RNA 受体，在识别和对 RNA 病毒感染的反应中发挥重要作用。我们还证明，通过删除 I 型干扰素（IFN）受体（IFNR1）在原代巨噬细胞中阻断 IFN 途径会导致 NDV 复制。在肿瘤细胞中，添加外源性 IFN-α4 可导致肿瘤生长减少和病毒复制抑制。最后，通过质粒转染增加肿瘤细胞中 RIG-I 的浓度与对 NDV 感染更强的抗性有关。这些发现为细胞溶质受体 RIG-I 和质膜受体 IFNR1 作为保护细胞免受 NDV 感染的关键分子发挥的关键作用提供了新的认识。
