A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKK epsilon

作者：Liang Deguang; Gao Yuan; Lin Xianzhi; He Zhiheng; Zhao Qinglan; Deng Qiang; Lan Ke^*

来源：Cell Research, 2011, 21(5): 793-806.

DOI：10.1038/cr.2011.5

• KSHV
• IFN
• IKK epsilon
• miR-K12-11

Type I interferon (IFN) signaling is the principal response mediating antiviral innate immunity. IFN transcription is dependent upon the activation of transcription factors IRF3/IRF7 and NF-kappa B. Many viral proteins have been shown as being capable of interfering with IFN signaling to facilitate evasion from the host innate immune response. Here, we report that a viral miRNA, miR-K12-11, encoded by Kaposi';s sarcoma-associated herpesvirus (KSHV) is critical for the modulation of IFN signaling and acts through targeting I-kappa-B kinase epsilon (IKK epsilon). Ectopic expression of miR-K12-11 resulted in decreased IKK epsilon expression, while inhibition of miR-K12-11 was found to restore IKK epsilon expression in KSHV-infected cells. Importantly, expression of miR-K12-11 attenuated IFN signaling by decreasing IKK epsilon-mediated IRF3/IRF7 phosphorylation and by inhibiting the activation of IKK epsilon-dependent IFN stimulating genes (ISGs), allowing miR-K12-11 suppression of antiviral immunity. Our data suggest that IKK epsilon targeting by miR-K12-11 is an important strategy utilized by KSHV to modulate IFN signaling during the KSHV lifecycle, especially in latency. We also demonstrated that IKK epsilon was able to enhance KSHV reactivation synergistically with the treatment of 12-O-tetradecanoylphorbol 13-acetate. Moreover, inhibition of miR-K12-11 enhanced KSHV reactivation induced by vesicular stomatitis virus infection. Taken together, our findings also suggest that miR-K12-11 can contribute to maintenance of KSHV latency by targeting IKK epsilon.

• 出版日期2011-5
• 单位中国科学院上海巴斯德研究所; 中国科学院上海生命科学研究院