Dengue Virus Impairs Mitochondrial Fusion by Cleaving Mitofusins

PLoS Pathogens

Yi-Ling Lin¹  Jian-Jong Liang¹  Chia-Yi Yu²  Michael M. C. Lai³  Wei-Jheng Huang³  Jin-Kun Li⁴  Chan-I Su⁴  Bi-Lan Chang⁴  Yi-Ling Lee⁴ 

[1] Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan;Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan;Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

关键词: Mitochondria;    Proteases;    Dengue virus;    Cell fusion;    Cell death;    Cell staining;    Apoptosis;    Membrane fusion;   

DOI  :  10.1371/journal.ppat.1005350

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Mitochondria are highly dynamic subcellular organelles participating in many signaling pathways such as antiviral innate immunity and cell death cascades. Here we found that mitochondrial fusion was impaired in dengue virus (DENV) infected cells. Two mitofusins (MFN1 and MFN2), which mediate mitochondrial fusion and participate in the proper function of mitochondria, were cleaved by DENV protease NS2B3. By knockdown and overexpression approaches, these two MFNs showed diverse functions in DENV infection. MFN1 was required for efficient antiviral retinoic acid-inducible gene I–like receptor signaling to suppress DENV replication, while MFN2 participated in maintaining mitochondrial membrane potential (MMP) to attenuate DENV-induced cell death. Cleaving MFN1 and MFN2 by DENV protease suppressed mitochondrial fusion and deteriorated DENV-induced cytopathic effects through subverting interferon production and facilitating MMP disruption. Thus, MFNs participate in host defense against DENV infection by promoting the antiviral response and cell survival, and DENV regulates mitochondrial morphology by cleaving MFNs to manipulate the outcome of infection.

【 授权许可】

CC BY