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鉴定一种具有潜在降低致癌性的新型人乳头瘤病毒16型E1基因变体。

Identification of a novel human papillomavirus type 16 E1 gene variant with potentially reduced oncogenicity.

作者信息

Sabol Ivan, Matovina Mihaela, Gasperov Nina Milutin, Grce Magdalena

机构信息

Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.

出版信息

J Med Virol. 2008 Dec;80(12):2134-40. doi: 10.1002/jmv.21304.

DOI:10.1002/jmv.21304
PMID:19040290
Abstract

The human papillomavirus (HPV) 16 genome has been studied extensively, although no study has focused on the E1 gene that is implicated in viral DNA replication. After analyzing the E1 region of HPV 16 genomes in 429 cervical samples, 11.2% were found to contain a 63 nucleotides duplication in this region. Sequence analysis of the E6 and the E7 regions has shown that all samples containing this duplication were related to E6-G350 variant of the HPV 16 (Chi square test, P = 0.0012). A comparison of cervical lesion severity of the examinees having regular or variant E1 genes has shown that the variant group had a significantly (Fischer's exact test, P = 0.0401) lower percentage of high grade disease cases, suggesting that this particular duplication might reduce the oncogenic potential of HPV 16, and also might clarify the differences of E6-G350 variant oncogenicity observed in European populations. Albeit, a decreased incidence of high grade cervical lesions can be linked to the prevalence of multiple HPV infection, the additional decrease of those cases with the variant E1 gene versus those without (10.5% and 18.6%, respectively) can only be ascribed to the effect of this particular HPV variant. Further research is needed to clarify the biology of these HPV 16 E1 variants.

摘要

人乳头瘤病毒(HPV)16型基因组已得到广泛研究,不过尚无研究聚焦于与病毒DNA复制相关的E1基因。在分析了429份宫颈样本中HPV 16基因组的E1区域后,发现11.2%的样本在该区域存在63个核苷酸的重复。对E6和E7区域的序列分析表明,所有含有这种重复的样本均与HPV 16的E6 - G350变体相关(卡方检验,P = 0.0012)。对具有正常或变体E1基因的受检者宫颈病变严重程度进行比较后发现,变体组的高级别疾病病例百分比显著更低(费舍尔精确检验,P = 0.0401),这表明这种特定的重复可能会降低HPV 16的致癌潜力,也可能会阐明在欧洲人群中观察到的E6 - G350变体致癌性的差异。尽管高级别宫颈病变发病率的降低可能与多种HPV感染的流行有关,但与没有变体E1基因的病例相比,有变体E1基因的病例中高级别病变病例的额外减少(分别为10.5%和18.6%)只能归因于这种特定HPV变体的影响。需要进一步研究来阐明这些HPV 16 E1变体的生物学特性。

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