The E1 Protein of Human Papillomavirus Type 16 Is Dispensable for Maintenance Replication of the Viral Genome
The E1 Protein of Human Papillomavirus Type 16 Is Dispensable for Maintenance Replication of the Viral Genome
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DOI：
10.1128/jvi.06450-11
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发表时间：
2012-03-01
影响因子：
5.4
通讯作者：
Kiyono, Tohru
中科院分区：
文献类型：
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作者：
Egawa, Nagayasu;Nakahara, Tomomi;Kiyono, Tohru
乳头瘤病毒基因组被认为在感染后很快扩增到每个细胞约100个拷贝，在基底细胞中保持恒定在该水平，并在角质形成细胞分化时扩增用于病毒产生。为了确定在病毒DNA复制的不同阶段对E1的需求，使用了人乳头瘤病毒16型（HPV 16）基因组的E1缺陷突变体，其特征在于E1基因中的翻译终止突变。在有或没有E1外源表达的情况下，监测突变HPV 16基因组作为核附加体复制的能力。与野生型基因组不同，E1缺陷型HPV 16基因组在外源性E1表达的存在下仅作为附加体在人角质形成细胞中建立。一旦建立，它可以复制与野生型基因组相同的效率，即使在外源E1被删除。然而，在钙诱导的角质形成细胞分化，再次扩增依赖于外源性E1。这些结果表明，E1蛋白是维持复制，但不是初始和生产性复制的HPV 16。
Papillomavirus genomes are thought to be amplified to about 100 copies per cell soon after infection, maintained constant at this level in basal cells, and amplified for viral production upon keratinocyte differentiation. To determine the requirement for E1 in viral DNA replication at different stages, an E1-defective mutant of the human papillomavirus 16 (HPV16) genome featuring a translation termination mutation in the E1 gene was used. The ability of the mutant HPV16 genome to replicate as nuclear episomes was monitored with or without exogenous expression of E1. Unlike the wild-type genome, the E1-defective HPV16 genome became established in human keratinocytes only as episomes in the presence of exogenous E1 expression. Once established, it could replicate with the same efficiency as the wild-type genome, even after the exogenous E1 was removed. However, upon calcium-induced keratinocyte differentiation, once again amplification was dependent on exogenous E1. These results demonstrate that the E1 protein is dispensable for maintenance replication but not for initial and productive replication of HPV16.