WTAP-Mediated m6A Modification of IFNE is Required for Antiviral Defense in Condyloma Acuminata

• Published in: Journal of dermatological science Vol. 111; no. 2; pp. 43 - 51
• Main Authors: Gu, Zhichao, Liu, Jiaying, Qin, Lei, Zhang, Yong, Cui, Wenya, Huang, Huayu, Liu, Lian, Cao, Yuchun, Zhang, Huafeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2023
• Subjects: antiviral responses; Condylomata acuminata; IFNE; m6A modification; WT1-associated protein (WTAP); FTO; YTHDC; YTHDF1; m6A modification; WTAP; HSV; MeRIP; STIs; HPV; ALKBH5; HIV; WT1-associated protein (WTAP); IFNE; Condylomata acuminata; m6A; antiviral responses; IFN-ε; METTL3/14; CA; HaCaT; MA modification; Antiviral responses
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2023.07.004

IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation. In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR. In this study, we identified IFN-ɛ was markedly upregulated (~5 fold) in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=-0.4646, P=0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA. Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts. •HPV infection induces IFN-ɛ expression in keratinocytes•IFN-ɛ shows negative correlation with the development of condyloma acuminata•IFN-ɛ suppressed the susceptibility of HPV infection•WTAP regulates the expression of IFN-ɛ by m6A modification