Yang Yang, Wang Hexiao, Zhang Xinrui, Huo Wei, Qi Ruiqun, Gao Yali, Zhang Gaofeng, Song Bing, Chen Hongduo, Gao Xinghua
Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, China.
Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, China; Regenerative Medicine, Cardiff Institute of Tissue Engineering and Repair, School of Dentistry, Cardiff University, Cardiff, UK.
J Invest Dermatol. 2017 Apr;137(4):810-818. doi: 10.1016/j.jid.2016.06.635. Epub 2016 Nov 24.
Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been identified as potent viral DNA mutators and have broad antiviral activity. In this study, we demonstrated that apolipoprotein B mRNA-editing catalytic polypeptide 3A (A3A) and A3G expression levels were significantly upregulated in human papillomavirus (HPV)-infected cell lines and tissues. Heat treatment resulted in elevated expression of A3A and A3G in a temperature-dependent manner in HPV-infected cells. Correspondingly, HPV-infected cells heat-treated at 44 °C showed accumulated G-to-A or C-to-T mutation in HPV E2 gene. Knockdown of A3A or A3G could promote cell viability, along with the lower frequency of A/T in HPV E2 gene. In addition, regressing genital viral warts also harbored high G-to-A or C-to-T mutation in HPV E2 gene. Taken together, we demonstrate that apolipoprotein B mRNA-editing catalytic polypeptide 3 expression and editing function was heat sensitive to a certain degree, partly explaining the mechanism of action of local hyperthermia to treat viral warts.
载脂蛋白B信使核糖核酸编辑催化多肽（APOBEC）3蛋白已被鉴定为强效病毒DNA诱变剂，并具有广泛的抗病毒活性。在本研究中，我们证明，在人乳头瘤病毒（HPV）感染的细胞系和组织中，载脂蛋白B信使核糖核酸编辑催化多肽3A（A3A）和A3G的表达水平显著上调。热处理导致HPV感染细胞中A3A和A3G的表达以温度依赖的方式升高。相应地，在44℃进行热处理的HPV感染细胞在HPV E2基因中出现G到A或C到T突变的累积。敲低A3A或A3G可提高细胞活力，同时HPV E2基因中A/T的频率降低。此外，消退期的生殖器病毒疣在HPV E2基因中也存在高比例的G到A或C到T突变。综上所述，我们证明载脂蛋白B信使核糖核酸编辑催化多肽3的表达和编辑功能在一定程度上对热敏感，这部分解释了局部热疗治疗病毒疣的作用机制。
