Dengue virus impairs mitochondrial fusion by cleaving mitofusins (PLoS Pathog 11:e1005350, 2015)

報告日期: 2016/03/15
報告時間: 5:10/6:00
報告學生: 賴彥仲
講評老師: 余佳益

Dengue Virus Impairs Mitochondrial Fusion by Cleaving Mitofusins

Chia-Yi Yu, Jian-Jong Liang, Jin-Kun Li, Yi-Ling Lee, Bi-Lan Chang, Chan-I Su, Wei-Jheng Huang, Michael M. C. Lai, Yi-Ling Lin

PLoS Pathog. 2015 Dec 30;11(12):e1005350.

Speaker: Yen-Chung Lai (賴彥仲)            Time: 17:00 ~18:00, Mar 15, 2016

Commentator: Chia-Yi Yu, Ph.D (余佳益)   Place: 醫學院 602


Dengue virus (DENV) causes the leading arthropod-transmitted viral infection of tropics and subtropics, which threatens billions of people in the world. Due to the pathogenesis of dengue is not totally revealed, there are still no desirable vaccine nor anti-viral drugs available now. Mitochondria are cellular power producer, which maintain multiple physiological homeostasis such as ATP production, fatty acid synthesis, and programmed cell death. In addition to energy provider, accumulated studies demonstrated that mitochondria also trigger antiviral RLR-signaling to act as defender against viral infection [1]. In this study, two mitofusins, MFN1 and MFN2, but not fission proteins are identified to be cleavage by DENV protease, NS2B3, during DENV infection which disrupt mitochondrial dynamic to benefit viral replication. By overexpression and knockdown approaches, MNF1 and MNF2 showed diverse defensive roles during DENV infection. MNF1 activates innate immunity and induces interferon production to suppress viral replication while MNF2 attenuates DENV-induced MMP disruption and caspase dependent cell death to support cell survival. Thus, the cleavage of both MNFs attenuate host innate defense response and increase cell death of DENV-infected cells. Taken together, this study provided a new insight into interplay of weapon of DENV and host innate defense system, and provided a potential target to control dengue disease.


  1. Seth, R.B., et al., Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 2005. 122(5): p. 669-82.