自主知识产权的局部温热疗法治疗人乳头瘤病毒感染性皮肤病观察到良好临床疗效，治疗一处靶疣使得远隔非干预部位的其他疣体也会脱落，提示温热可诱导机体产生抗病毒的系统性免疫，但具体免疫诱导机制不明。前期数据显示HSP40家族DNAJA4在温热过程中发生明确改变，该基因可以影响到一系列涉及MHC I、CD8+T细胞免疫的相关分子表达。本研究拟以角质形成细胞、HPV基因整合细胞系、温热干预的疣体组织为研究对象，以DNAJA4为核心，研究DNAJA4所结合的相互作用蛋白、温热通过DNAJA4影响与HPV早期蛋白E7相互作用的M2-PK的构象、亚型、形成MHC I类胞内抗原复合物的情况，进而刺激细胞毒性T细胞活化，并在临床样本中进行验证。明确发挥作用的关键分子间的相互作用，努力寻找可以方便人工干预的增强机体抗病毒免疫作用的靶标分子，深入认识温热诱导抗病毒免疫机制。

Local hyperthermia to treat cutaneous human papilloma virus infection using thermotherapeutic device with independent intellectual property rights has been eutherapeutic during clinical application. During thermotherapy, the non-targeted, distal cutaneous lesions were cured as well as directly targeted lesion, prompting an underlying systemic immunological antiviral responding mechanism of the body, which remains to be further investigated. Our data shows that thermo-treatment changed the expression pattern of a HSP40 family member, DnaJA4, and thus further influenced a series of other immune-active components, like MHC-I and CD8+ CTL. This research concentrates on DnaJA4 to explore the protein-protein interaction, conformational and isoformal change of M2-PK through HPV-E7 interaction, and intracellular antigen- MHC-I complex formation which activate CD8+ thymocytes by using human keratinocytes, HPV transfected cell lines and thermo-treated clinical wart tissues. Furthermore, the research aims to define the interaction between key molecules and search for immunologic targets for artificial intervention, and bring further understandings into the mechanism of anti-viral immunity induced by local hyperthermia.