Different modes of human papillomavirus DNA replication during maintenance

Different modes of human papillomavirus DNA replication during maintenance
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DOI:
10.1128/jvi.80.9.4431-4439.2006
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发表时间:
2006-05-01
影响因子:
5.4
通讯作者:
Raj, K
Raj, K
中科院分区:
医学2区
文献类型:
--
作者:
Hoffmann, R;Hirt, B;Raj, K

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人乳头瘤病毒(HPV)通过感染上皮的基底细胞开始其生命周期。在这些增殖的细胞中,病毒基因组被复制、维持并传递给子细胞。使用HPV附加体含有细胞系,来自自然感染的宫颈组织,我们调查了病毒DNA在这些细胞中复制的模式。我们观察到,HPV16 DNA在W12细胞中以有序的每S期一次的方式复制,而HPV31 DNA在CIN612细胞中通过随机选择机制复制。然而,当将HPV 16和HPV 31 DNA分别引入另一种角质形成细胞系NIKS时,它们都随机复制。这表明HPV DNA固有地能够通过随机选择或每S期一次的机制复制,并且HPV DNA复制的模式取决于携带病毒附加体的细胞。病毒复制蛋白E1在W12细胞中的高表达将HPV 16 DNA复制转化为随机选择复制,因此,似乎增殖细胞中HPV DNA复制的模式取决于宿主细胞中该蛋白的存在或增加的水平。这些观察维护,延迟和持久性的影响进行了讨论。
Human papillomavirus (HPV) begins its life cycle by infecting the basal cells of the epithelium. Within these proliferating cells, the viral genomes are replicated, maintained, and passed on to the daughter cells. Using HPV episome-containing cell lines that were derived from naturally infected cervical tissues, we investigated the mode by which the viral DNAs replicate in these cells. We observed that, whereas HPV16 DNA replicated in an ordered once-per-S-phase manner in W12 cells, HPV31 DNA replicated via a random-choice mechanism in CIN612 cells. However, when HPV16 and HPV31 DNAs were separately introduced into an alternate keratinocyte cell line NIKS, they both replicated randomly. This indicates that HPV DNA is inherently capable of replicating by either random-choice or once-per-S-phase mechanisms and that the mode of HPV DNA replication is dependent on the cells that harbor the viral episome. High expression of the viral replication protein E1 in W12 cells converted HPV16 DNA replication to random-choice replication and, as such, it appears that the mode of HPV DNA replication in proliferating cells is dependent on the presence or the increased level of this protein in the host cell. The implications of these observations on maintenance, latency, and persistence are discussed.