自主创新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HSP70家族分子HSPA6在温热过程中发生显著改变，进一步核酸和蛋白高通量数据显示该基因可以影响AP-1家族分子，并可能影响几方面抗病毒免疫相关分子表达。本研究拟以角质形成细胞、HPV基因整合细胞、温热干预的疣体组织、HPV小鼠模型为研究对象，以HSPA6与AP-1作用机制、AP-1对下游抗HPV感染相关因子的影响等为重点研究内容，明确数个关键分子间的相互作用及作用方式，阐释温热诱导HPV病毒免疫诱导的机制。该研究将有助于寻找人工干预增强机体抗病毒免疫的作用靶标分子，进一步在现有临床疗效的基础上，增强抗病毒免疫的强度，缩短治疗干预时间，为其他抗感染免疫、疫苗开发、佐剂设计等提供借鉴。

Potent therapeutical effect of local hyperthermia against HPV-infectious cutaneous diseases using patent local hyperthermal device was observed. The fact that the simultaneous curation of distant lesions in the body of the same patinet without direct hyperthermal treatment suggested that hyperthermal therapy may induce systemic anti-HPV immunity, the underlying mechanism of which, however, remained an enigma. Data from our recent work had shown that HSP70 family member HSPA6 was transcriptionally and translationally altered during hyperthermia. Based on subsequent high-throughput examination and bioinformatical analysis, we speculated that HSPA6 may influence the expression of AP-1 proteins and thereby affect the expression of downstream molecules involved in anti-virus activity. In this study we used keratinocytes, HPV(+) epidermal cells, hyperthermia-intervened wart tissues and HPV-infected mouse model to investigate the actions of HSPA6 and AP-1 in hyperthermia-induced anti-HPV immunity and try to find the interactions of the key molecules involved, so as to look for target molecules to boost the efficacy of hyperthermia therapy, shorten therapeutic time span and provide insigts for further studies in anti-HPV immunity, vaccine development and adjuvant design.