Defective Interfering Viral Particles in Acute Dengue Infections
Defective Interfering Viral Particles in Acute Dengue Infections
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DOI：
10.1371/journal.pone.0019447
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Aaskov, John
中科院分区：
文献类型：
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作者：
Li, Dongsheng;Lott, William B.;Aaskov, John
虽然RNA病毒中的许多遗传变异是由于其RNA依赖性RNA聚合酶的易错性而产生的，但重组可能会导致更大的变化。遗传变化的一个极端例子是在有缺陷的干扰（DI）病毒颗粒中发现的，其中亲本病毒基因组的大部分已被删除，残留的亚基因组片段通过共感染功能病毒的互补而复制。虽然DI颗粒的大多数报告都涉及体外研究，但有一些证据表明在体内慢性病毒感染中存在DI颗粒。在这项研究中，从感染四种DENV血清型中任何一种的患者血清中回收了仅在基因组的3'和5'末端含有关键调控元件的登革病毒（DENV）RNA的短片段。在通过添加登革热患者血清感染的伊蚊细胞培养物的上清液中检测到相同的RNA片段，这表明亚基因组RNA可能以缺陷型干扰（DI）病毒颗粒在人和蚊子宿主之间传播。在体外转录的亚基因组RNA对应于在体内检测到的亚基因组RNA可以在野生型病毒存在下包装在病毒样颗粒中，并在细胞培养物中传播至少三代。富集这些推定的DI颗粒的DENV制剂在C6-36细胞的共感染后降低了野生型登革病毒的产量。这是自然界中首次报道急性虫媒病毒感染中的DI颗粒。这里描述的内部基因组缺失是在DENV中观察到的最广泛的缺陷，并且可能是由缺陷病毒介导的更广泛的疾病减毒过程的一部分。
While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.