Variant upstream regulatory region sequences differentially regulate human papillornavirus type 16 DNA replication throughout the viral life cycle
Variant upstream regulatory region sequences differentially regulate human papillornavirus type 16 DNA replication throughout the viral life cycle
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DOI：
10.1128/jvi.79.10.5914-5922.2005
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Hubert, WG
中科院分区：
文献类型：
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作者：
Hubert, WG
虽然病毒上游调控区（URR）在人乳头瘤病毒（HPV）生命周期中的核心作用已得到充分证实，但其对病毒复制因子表达和HPV 16型（HPV 16）质粒复制的影响仍不清楚。HPV 16的一些非原型变体含有改变的URR序列，并被认为增加了感染的致癌风险。为了确定病毒复制和变异URR之间的关系，用可复制的HPV 16原型W12构建杂合病毒基因组，并在重现正常病毒复制的不同阶段的测定中进行分析。杂交HPV 16基因组的建立效率在欧洲原型和来自非洲和美洲的变体之间相差约20倍。一般来说，欧洲和非洲的基因组表现出最低的复制效率。在美国变异体中观察到的高复制水平主要归因于其复制因子E1和E2的有效表达。这些病毒基因组的维持水平变化约5倍，这与它们各自的建立表型和已发表的P，，活性相关。在复制型HPV 16基因组中也可观察到营养性DNA扩增。这些结果表明，有效的E1/E2的表达和质粒复制水平升高，在感染的持续阶段可能包括HPV 16介导的肿瘤发生的危险因素。
While the central role of the viral upstream regulatory region (URR) in the human papillomavirus (HPV) life cycle has been well established, its effects on viral replication factor expression and plasmid replication of HPV type 16 (HPV16) remain unclear. Some nonprototypic variants of HPV16 contain altered URR sequences and are considered to increase the oncogenic risk of infections. To determine the relationship between viral replication and variant URRs, hybrid viral genomes were constructed with the replication -competent HPV16 prototype W12 and analyzed in assays which recapitulate the different phases of normal viral replication. The establishment efficiencies of hybrid HPV16 genomes differed about 20-fold among European prototypes and variants from Africa and America. Generally, European and African genomes exhibited the lowest replication efficiencies. The high replication levels observed with American variants were primarily attributable to their efficient expression of the replication factors E1 and E2. The maintenance levels of these viral genomes varied about fivefold, which correlated with their respective establishment phenotypes and published P,, activities. Vegetative DNA amplification could also be observed with replicating HPV16 genomes. These results indicate that efficient E1/E2 expression and elevated plasmid replication levels during the persistent stage of infection may comprise a risk factor in HPV16-mediated oncogenesis.