Dengue virus targets the adaptor protein MITA to subvert host innate immunity (PLoS Pathogens, 2012, 8(6):e1002780)

報告日期: 2012/10/16
報告時間: 17:10/18:00
報告學生: 吳彥緯
講評老師: 王淑鶯
附件下載: 下載[1220-1348566549-1.pdf] 

Dengue Virus Targets the Adaptor Protein MITA to Subvert Host Innate Immunity

Chia-Yi Yu, Tsung-Hsien Chang, Jian-Jong Liang, Ruei-Lin Chiang, Yi-Ling Lee, Ching-Len Liao, Yi-Ling Lin. PLoS Pathogens, 8, 1–13 (2012).

Speaker: Yan-Wei Wu(吳彥緯)                                    Time: 17:10~18:00, Oct. 16, 2012

                   Commentator: Shu-Ying Wang, Ph.D.(王淑鶯老師)   Place: Room 602

Abstract

 

Infection of pathogens induces innate immune responses by many pattern recognition receptors (PRRs). These PRRs, such as toll-like receptors, RIG-I, MDA5 and so on, are found to be involved in innate immune responses. Mediater of IRF3 activation MITA1 interacting with RIG-I is involved in viral replication triggered interferon production2. However, pathogens may disrupt the signal transduction pathway for survival. In this study, the authors found that the activation of interferon regulatory factor 3 (IRF3) by dsRNA and dsDNA was blocked by dengue viral protease, NS2B3. Compared to other PRRs, only MITA was degraded by NS2B3. Either N or C termial of MITA was cleaved by NS2B3 and its function was impaired. Interestingly, MPYS, the murine homologue of MITA, was not cleaved by NS2B3. Therefore, dengue replication could induce IRF3 activation in MPYS-expressing cells but not in MITA-expressing cells. Furthermore, shRNA targeting MITA increased dengue replication and decreased interferon in conditioned medium from A549 cells. Besides, intracellular puncta of MITA activation was not formed with NS2B3 expression. In contrast to poly(I:C), treatment with poly(dA:dT) enhanced the interaction between MITA and NS2B3. In conclusion, the authors demonstrated that MITA is the target of dengue protease NS2B3 for disruption of host innate immune responses. A hint is given that therapy against NS2B3 may suppress dengue replication and restore interferon production.

 

 

References:

 

1. Zhong, B., et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29, 538-550 (2008).

2. Ishikawa, H., Ma, Z. & Barber, G.N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788-792 (2009).