德国癌症研究中心3日发表公报说，该中心研究人员发现了宫颈癌病毒破坏人体免疫力的机理——这种病毒能抑制人体免疫系统中一种信号分子的基因表达。这一发现将有助于研究人员寻找医治宫颈癌的新方法。
人乳头瘤病毒16型是引发宫颈癌的最常见病毒。德国癌症研究中心的科研人员通过观察培养皿中被这种病毒感染的细胞发现，这种病毒的E6基因在宿主细胞中抑制了其免疫系统信号物质IFNk干扰素的基因表达。研究人员随后在宫颈癌组织样本上做实验也验证了这一发现。
干扰素是细胞在受到病毒感染后分泌的具有抗病毒功能的蛋白质。细胞感染病毒后分泌的干扰素能对周围未感染细胞上的相关受体产生作用，促使这些细胞合成抗病毒蛋白质防止进一步感染。
研究人员指出，IFNk干扰素能抵抗人乳头状瘤病毒，是因为它主要在这种病毒寄居的上皮细胞中产生。如果这些细胞中的IFNk干扰素失灵，则参与免疫的其他蛋白质也会功能失调。
研究人员计划下一步研究为人体输入IFNk干扰素，看是否可以抑制宫颈癌细胞的生长。
这一成果已发表在美国《癌症研究》杂志上。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Research 69, 8718, November 15, 2009.doi: 10.1158/0008-5472.CAN-09-0550
Epigenetic Silencing of Interferon-κ in Human Papillomavirus Type 16–Positive Cells
Bladimiro Rincon-Orozco1, Gordana Halec2, Simone Rosenberger1, Dorothea Muschik1, Ingo Nindl1, Anastasia Bachmann3, Tina Maria Ritter1, Bolormaa Dondog4, Regina Ly1, Franz X. Bosch2, Rainer Zawatzky1 and Frank R?sl1
1 Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Universit?t Heidelberg; 2 Molekularbiologisches Labor, Universit?ts-HNO-Klinik Heidelberg; 3 Molecular Alcohol Research in Gastroenterology, Universit?t Heidelberg; and 4 Angewandte Tumorvirologie, Abteilung Genomver?nderungen und Karzinogenese, Deutsches Krebsforschungszentrum, Heidelberg, Germany
We have investigated interferon-κ (IFN-κ) regulation in the context of human papillomavirus (HPV)–induced carcinogenesis using primary human foreskin keratinocytes (HFK), immortalized HFKs encoding individual oncoproteins of HPV16 (E6, E7, and E6/E7), and cervical carcinoma cells. Here, IFN- κ was suppressed in the presence of E6, whereas its expression was not affected in HFKs or E7-immortalized HFKs. Transcription could be reactivated after DNA demethylation but was decreased again upon drug removal. Partial reactivation could also be accomplished when E6 was knocked down, suggesting a contribution of E6 in IFN-κ de novo methylation. We identified a single CpG island near the transcriptional start site as being involved in selective IFN-κ expression. To prove the functional relevance of IFN-κ in building up an antiviral response, IFN-κ was ectopically expressed in cervical carcinoma cells where protection against vesicular stomatitis virus–mediated cytolysis could be achieved. Reconstitution of IFN-κ was accompanied by an increase of p53, MxA, and IFN-κ regulatory factors, which was reversed by knocking down either IFN-κ or p53 by small interfering RNA. This suggests the existence of a positive feedback loop between IFN-κ, p53, and components of IFN signaling pathway to maintain an antiviral state. Our in vitro findings were further corroborated in biopsy samples of cervical cancer patients, in which IFN-κ was also downregulated when compared with normal donor tissue. This is the first report showing an epigenetic silencing of type I IFN after HPV16 oncogene expression and revealing a novel strategy on how high-risk HPVs can abolish the innate immune response in their genuine host cells.
