Isolation of a human papillomavirus from a patient with epidermodysplasia verruciformis: presence of related viral DNA genomes in human urogenital tumors.
Isolation of a human papillomavirus from a patient with epidermodysplasia verruciformis: presence of related viral DNA genomes in human urogenital tumors.
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从疣状表皮发育不良患者中分离人乳头瘤病毒：人泌尿生殖肿瘤中存在相关病毒 DNA 基因组。
DOI：
10.1073/pnas.79.14.4437
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发表时间：
1982
影响因子：
11.1
通讯作者：
Switlyk,SA
中科院分区：
文献类型：
--
作者：
Green,M;Brackmann,KH;Sanders,PR;Loewenstein,PM;Freel,JH;Eisinger,M;Switlyk,SA
人乳头瘤病毒 (HPV) 的 DNA 基因组（暂定名为 HPV-EV）是从一名疣状表皮发育不良患者的手部到腿部病变处进行分子克隆的，这是一种慢性皮肤病，与 30% 的癌症风险相关。使用严格的杂交条件，我们观察到 HPV-EV 与 HPV-1、HPV-4、HPV-5 和 HPV-5a 的克隆基因组之间的同源性低于 5%。 HPV-EV DNA 显示与 HPV-2 大约 6% 同源性，与 HPV-3 大约 36% 同源性。这些数据表明 HPV-EV 与 HPV-3 部分相关。在 Southern blot 杂交实验中，使用 32P 标记的克隆 HPV-EV 作为探针，我们在分离 HPV-EV 的患者外阴原位癌（Bowenoid 病变）中检测到 HPV-EV 相关 DNA。在 10 例外阴癌中的 2 例和 31 例宫颈癌中的 2 例中检测到 HPV-EV 相关 DNA。在两名尖锐湿疣（肛门生殖器疣）患者的乳头状瘤中均发现了相关的 DNA 序列，考虑到据报道尖锐湿疣偶尔会转化为癌，这一点很有趣。阳性外阴DNA还用其他克隆的HPV DNA进行了探测：未检测到HPV-1、HPV-4和HPV-5a相关序列； HPV-3 和 HPV-2 DNA 探针分别检测到强 DNA 条带和弱 DNA 带，其大小与 HPV-EV 中发现的相同。 HPV DNA序列主要以游离病毒DNA分子的形式存在于阳性肿瘤中；没有发现整合到细胞 DNA 中的证据。乳头瘤病毒的新生物学图像是，被这些病毒转化的细胞通过游离的游离基因组维持在转化状态。因此，我们的研究结果与 HPV 通过类似机制在人类癌症中发挥作用的观点一致，但绝不证实。
The DNA genome of a human papillomavirus (HPV), tentatively designated HPV-EV, was molecularly cloned from hand to leg lesions of a patient with epidermodysplasia verruciformis, a chronic skin disease associated with a 30% risk of developing cancer. Using stringent hybridization conditions, we observed less than 5% homology between HPV-EV and the cloned genomes of HPV-1, HPV-4, HPV-5, and HPV-5a. HPV-EV DNA showed approximately 6% homology with HPV-2 and 36% homology with HPV-3. These data suggest that HPV-EV is partially related to HPV-3. Using 32P-labeled cloned HPV-EV as probe in Southern blot hybridization experiments, we detected HPV-EV-related DNA in the carcinoma in situ (Bowenoid lesion) of the vulva of the patient from which HPV-EV was isolated. HPV-EV-related DNA was detected in 2 of 10 vulva carcinomas and in 2 of 31 cervical carcinomas. Related DNA sequences were found in papillomas from each of two patients with condyloma acuminata (anogenital warts), which is of interest considering that condylomas have been reported to convert occasionally to carcinomas. The positive vulva DNAs were also probed with other cloned HPV DNAs: HPV-1, HPV-4, and HPV-5a-related sequences were not detected; HPV-3 and HPV-2 DNA probes detected strong and weak DNA bands, respectively, of the same size as found with HPV-EV. The HPV DNA sequences were present in the positive tumors mainly as free viral DNA molecules; no evidence for integration into cellular DNA was found. The emerging biological picture with papillomaviruses is that cells transformed by these viruses are maintained in a transformed state by free episomal genomes. Thus, our findings are consistent with the idea, but by no means establish, that HPVs play a role in human cancer by a similar mechanism.