趋化因子CXCL14在宿主抵御人乳头瘤病毒HPV感染诱发癌症进程中的表达调控和作用机理

Cervical cancer ranked second in the global women's cancer; make a serious threat to human health. HPV infection is the major cause of cervical cancer. Only about 10-20% of HPV infections will ultimately turn into persistent infection, which suggesting that intrinsic immune mechanisms in the host will inhibit the replication of the virus and eventually eliminate HPV, but the mechanism is unclear. Our preliminary results suggest that HPV infection can inhibit CXCL14 expression and CXCL14 can clear the tumor by regulation of the cell immune response. The project will further clarify the mechanism of deregulation of CXCL14 expression by HPV infection. We also will study the role of CXCL14 in host innate immune response against HPV infection. We will screen small molecules/peptide to promote CXCL14 expression, and the ultimate goal is to reveal the expression and mechanism of CXCL14 in cancers caused by HPV infection, and find targets for developing new cancer drugs.

宫颈癌发病率在全球女性恶性肿瘤发生中居第二位，严重威胁人类健康。HPV感染是导致宫颈癌发生的主要原因。HPV感染人群内大约只有10-20%的感染会最终转化为持续感染，这表明宿主体内的内在免疫机制会抑制病毒的复制并最终清除HPV, 但其具体的作用机制远未清晰。我们前期的研究结果表明HPV感染会显著抑制CXCL14的表达，并且CXCL14具有通过调控免疫细胞反应清除肿瘤的作用机制。本项目将进一步阐明HPV感染抑制CXCL14表达的调控机制，CXCL14在先天免疫细胞抵抗病毒方面的调控作用，并筛选对CXCL基因表达起促进作用的小分子物质/活性多肽，最终目标是揭示CXCL14在HPV感染导致的癌症中的表达和作用机理，为靶向抗癌药物开发奠定基础。

HPV感染人群内大约只有10-20%的感染会最终转化为持续感染以及癌症，这表明宿主体内的内在免疫机制会抑制病毒的复制并最终清除病毒, 其具体作用机制尚且不清楚，这是我们课题的关注重点。我们的研究结果明确了CXCL14在宿主控制HPV感染中发挥重要功能，在细胞和动物水平，系统检测了病毒感染诱导宿主细胞先天免疫反应。通过机制研究探寻调控病毒感染的靶标分子并筛选鉴定了调控炎症反应的候选小分子药物。研究成果在NI和JCI等国际期刊发表研究论文5篇，揭示了病毒感染诱导宿主免疫应答的的表达调控和作用机理。