Ebola virus defective interfering particles and persistent infection
Ebola virus defective interfering particles and persistent infection
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DOI：
10.1006/viro.1999.9915
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发表时间：
1999-09-15
期刊：
影响因子：
3.7
通讯作者：
Nichol, ST
中科院分区：
文献类型：
--
作者：
Calain, P;Monroe, MC;Nichol, ST
埃博拉病毒（扎伊尔亚型）与高死亡率疾病暴发有关，通常涉及人际传播。存活的患者可以显示病毒持续存在时间延长的证据。研究了埃博拉病毒在组织培养中产生缺陷干扰（DI）颗粒并建立持续感染的可能性。发现连续未稀释的病毒传代迅速导致产生具有缺失和回拷型DI基因组重排的病毒微复制子的进化群体。第十次未稀释病毒传代导致建立病毒持续感染的细胞系。在一次或两次危机后，这些细胞稳定维持数月，并持续脱落感染性病毒。对选定的一组埃博拉病毒微复制子和标准丝状病毒的估计基因组长度的分析显示，没有明显的基因组长度规则，例如在与病毒遗传学相关的副粘病毒亚科病毒中发现的“六规则”。基于分析的天然存在的微复制子中保留的真实末端的长度，发现埃博拉病毒复制的最小启动子分别包含在基因组和反基因组RNA 3'末端的156和177个核苷酸区域内。此外，使用从持续感染的细胞释放的病毒的UV照射制剂，证明埃博拉病毒DI颗粒可以潜在地用作天然微复制子以测定标准病毒支持功能。
Ebola virus (Zaire subtype) is associated with high mortality disease outbreaks that commonly involve human to human transmission. Surviving patients can show evidence of prolonged virus persistence. The potential for Ebola virus to generate defective interfering (DI) particles and establish persistent: infections in tissue culture was investigated. It was found that serial undiluted virus passages quickly resulted in production of an evolving population of virus minireplicons possessing both deletion and copyback type DI genome rearrangements. The tenth undiluted virus passage resulted in the establishment of virus persistently infected cell lines. Following one or two crises, these cells were stably maintained for several months with continuous shedding of infectious virus. An analysis of the estimated genome lengths of a selected set of the Ebola virus minireplicons and standard filoviruses revealed no obvious genome length rule, such as "the rule of six" found for the phylogenetically related Paramyxovirinae subfamily viruses. Minimal promoters for Ebola virus replication were found to be contained within 156 and 177 nucleotide regions of the genomic and antigenomic RNA 3' termini, respectively, based on the length of authentic termini retained in the naturally occurring minireplicons analyzed. In addition, using UV-irradiated preparations of virus released from persistently infected cells, it was demonstrated that Ebola virus DI particles could potentially be used as natural minireplicons to assay standard virus support functions.