High-risk human papillomaviruses (HPVs) cause 5% of human cancers. Despite the availability of HPV vaccines, there remains a strong urgency to find ways to treat persistent HPV infections, as current HPV vaccines are not therapeutic for individuals already infected. We used a mouse papillomavirus infection model to characterize virus-host interactions. We found that mouse papillomavirus (MmuPV1) suppresses host immune responses via overexpression of stress keratins. In mice deficient for stress keratin K17 (K17KO), we observed rapid regression of papillomas dependent on T cells. Cellular genes involved in immune response were differentially expressed in the papillomas arising on the K17KO mice correlating with increased numbers of infiltrating CD8+ T cells and upregulation of IFNγ-related genes, including CXCL9 and CXCL10, prior to complete regression. Blocking the receptor for CXCL9/CXCL10 prevented early regression. Our data provide a novel mechanism by which papillomavirus-infected cells evade host immunity and defines new therapeutic targets for treating persistent papillomavirus infections.

中文翻译：

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应力角蛋白17通过下调T细胞募集来增强乳头瘤病毒感染引起的疾病。

高风险的人乳头瘤病毒（HPV）导致5％的人类癌症。尽管有HPV疫苗可用，但仍然迫切需要找到治疗持续性HPV感染的方法，因为当前的HPV疫苗对已经感染的个体无法治疗。我们使用了小鼠乳头瘤病毒感染模型来表征病毒-宿主相互作用。我们发现，小鼠乳头瘤病毒（MmuPV1）通过过度表达应激角蛋白来抑制宿主免疫反应。在缺乏应激性角蛋白K17（K17KO）的小鼠中，我们观察到了依赖T细胞的乳头状瘤的快速消退。与免疫反应有关的细胞基因在K17KO小鼠的乳头状瘤中差异表达，这与CD8 + T细胞浸润的增加和IFNγ相关基因的上调相关，包括CXCL9和CXCL10，在完全回归之前。阻断CXCL9 / CXCL10的受体可防止早期消退。我们的数据提供了一种新的机制，通过该机制，乳头瘤病毒感染的细胞可逃避宿主免疫力，并确定了治疗持续性乳头瘤病毒感染的新治疗靶点。