The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-α
The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-α
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DOI：
10.1006/viro.2000.0584
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发表时间：
2000-11-25
期刊：
影响因子：
3.7
通讯作者：
McMillan, NAJ
中科院分区：
文献类型：
--
作者：
Barnard, P;Payne, E;McMillan, NAJ
现在已经充分认识到，宫颈癌是由某些人乳头瘤病毒（HPV）亚型感染引起的，虽然干扰素-α（IFN-α）用于治疗HPV感染的病变，但HPV似乎已经开发出一种避免IFN-α影响的方法。临床上，耐药似乎与E7癌蛋白的表达有关。在这里，我们研究了来自高危和低危乳头瘤病毒亚型的E7蛋白在细胞中表达对一系列干扰素-α反应的影响。2fTGH是一种在选择培养基中生长依赖于IFN-α的细胞系，在E7存在下生长明显较差，并且IFN-α对上皮细胞的抗增殖作用在E7表达后丧失。IFN-α的抗病毒作用在表达E7的细胞中被消除。对IFN-α反应的丧失被发现发生在高风险和低风险乳头瘤病毒中。最后，缺失HPV 16型E7蛋白的氨基酸21-24部分逆转阻遏。我们得出结论，E7抑制IFN-α的功能作用，并且该特性被测试的所有HPV亚型共享。(C)北京大学出版社.
It is now well recognized that cervical cancer is caused by infection with certain human papillomavirus (HPV) subtypes and while interferon-alpha (IFN-alpha) is used to treat HPV-infected lesions, HPV appears to have developed a means to avoid the effects of IFN-alpha. Clinically, resistance appears to be associated with the expression of the E7 oncoprotein. Here we investigated the effects of expression in cells of the E7 protein from high- and low-risk papillomavirus subtypes on a range of responses to IFN-alpha. 2fTGH, a cell line dependent on IFN-alpha for growth in selection medium, grew significantly less well in the presence of E7, and the antiproliferative effects of IFN-alpha upon epithelial cells was lost upon E7 expression. The antiviral effects of IFN-alpha were abrogated in E7-expressing cells. Loss of response to IFN-alpha was found to occur in both high- and low-risk papillomaviruses. Finally, deletion of amino acids 21-24 of HPV type 16 E7 protein partially reversed repression. We conclude that E7 inhibits the functional effects of IFN-alpha and that this property is shared by all HPV subtypes tested. (C) 2000 Academic Press.