人乳头瘤病毒(HPV)11/16E6/E7蛋白已被认为在病毒发病机理中至关重要。这项研究试图揭示HPV11/16E6/E7转染的角质形成细胞如何抑制外周血单核细胞(PBMC)中细胞因子分泌的潜在机制。在以非接触方式共培养HPV11/16E6/E7转染的角质形成细胞与PBMC时,我们观察到PBMC分泌的各种细胞因子明显减少。为了确定这种抑制是否由特定的常见分泌因子介导,我们对这些转染细胞进行了转录组测序。该分析在所有四种HPV转染的细胞中鉴定了53个常见的差异分泌基因。生物信息学分析表明这些基因主要参与免疫调节。定量PCR(qPCR)和大量文献综述的结果表明12个基因(ACE2,BMP3,BPIFB1,CLU,CST6,CTF1,HMGB2,MMP12,PDGFA,RNASE7,SULF2,TGM2),和7个基因的上调(CCL17,CCL22,FBLN1,PLAU,S100A7,S100A8,S100A9),可能在调节肿瘤免疫和对抗病原体感染方面至关重要,基因S100A8和S100A9,IL-17信号通路尤其值得注意。因此,HPV11/16E6/E7蛋白可能通过改变宿主分泌基因的表达来抑制免疫细胞的细胞因子分泌。对这些基因的进一步探索可能会对HPV感染的复杂动力学产生新的见解。
Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.