Characterization of defective viral RNA produced during persistent infection of vero cells with Murray Valley encephalitis virus
Characterization of defective viral RNA produced during persistent infection of vero cells with Murray Valley encephalitis virus
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DOI：
10.1128/jvi.72.3.2474-2482.1998
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发表时间：
1998-03-01
影响因子：
5.4
通讯作者：
Urosevic, N
中科院分区：
文献类型：
--
作者：
Lancaster, MU;Hodgetts, SI;Urosevic, N
在许多动物RNA病毒大量感染后，细胞培养物中很容易产生有缺陷的干扰病毒颗粒。由于它们基因组中携带的缺陷，它们的生命周期需要由亲本病毒提供的辅助功能来补充，这使得它们既依赖于亲本病毒，又与亲本病毒竞争。在许多情况下，这是这样的。可能会导致亲本病毒的裂解周期终止，从而导致持续感染。在本文中，我们首次描述了在持续感染黄病毒墨累谷脑炎病毒的 Vero 细胞中产生的截短或有缺陷的干扰病毒 RNA 的存在。虽然在急性感染的Vero细胞中没有检测到这些RNA，但它们的出现与持续感染的建立相一致，我们还首次表明，有缺陷的病毒RNA在细胞培养物和无细胞病毒复制系统中复制良好，表明它们可能在病毒RNA合成水平上干扰亲本病毒的复制。对于 NS1 蛋白的 N 末端，这些缺失符合框架，允许在持续感染的细胞中合成截短的 NS1 蛋白。除了在病毒粒子组装和释放水平上的主要干扰之外，这可能对病毒 RNA 合成水平上对亲本病毒的干扰产生进一步的影响。
Defective interfering viral particles are readily produced in cell culture after a high multiplicity of infection with many animal RNA viruses, Due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus, In many instances, this. may cause the abrogation of a lytic cycle of the parental virus, lending to a persistent infection, In this paper, we describe for the first time the presence of truncated or defective interfering viral RNAs produced in Vero cells persistently infected with the flavivirus Murray Valley encephalitis virus. While these RNAs have not been detected in acutely infected Vero cells, their appearance coincided with the establishment of persistent infection,We also show for the first time that the defective viral RNAs replicate well in both cell culture and cell-free virus replication systems, indicating that they may interfere with the replication of parental virus at the level of viral RNA synthesis, Significantly, structural analyses of these RNA species including nucleotide sequencing have revealed that they carry similar nucleotide deletions encompassing the genes coding for the prM and E proteins and various gene segments coding for the N terminus of the NS1 protein, These deletions are in frame, allowing the synthesis of truncated NS1 proteins to occur in persistently infected cells, This may have further implications for the interference with the parental virus at the level of viral RNA synthesis in addition to a major one at the level of virion assembly and release.