title: Dengue virus utilizes calcium modulating cyclophilin-binding ligand to subvert apoptosis.
abstract: Dengue virus (DENV) capsid (C) proteins are the major structural component of virus particles. This study aimed to identify the host interacting partners of DENV C protein that could contribute to viral pathogenesis. DENV C protein was screened against human liver cDNA yeast two-hybrid library. We identified calcium modulating cyclophilin-binding ligand (CAML) as a novel interacting partner of DENV C protein. We report for the first time that CAML influenced DENV production. DENV production was significantly attenuated in CAML knock-down cells at 36h post-infection. CAML did not influence DENV entry, genome uncoating, viral transcription, viral translation and virus secretion. Our study pinpointed that CAML influenced the process of apoptosis by altering mitochondrial membrane potential and caspase-3 activation from 36h post-infection. Over-expression of CAML protected Huh7 cells from apoptosis and knock down of CAML favoured apoptosis following infection with DENV. We also showed that CAML expression was up-regulated during DENV infection. Increased CAML levels protected DENV-infected cells from undergoing apoptosis by preventing mitochondrial damage and caspase-3 activation which in turn favoured DENV production from 36h post-infection. Overall, this study demonstrated that DENV manipulated the levels of CAML to subvert the apoptotic process which in turn favoured efficient virus production.
authors.affiliation: Department of Internal Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.forename: Rongjie
authors.initials: R
authors.lastname: Huang
authors.forename: Weiyong
authors.initials: W
authors.lastname: Liao
authors.forename: Zhaoni
authors.initials: Z
authors.lastname: Chen
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D003715:Dengue / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; D036022:Capsid Proteins; D012367:RNA, Viral; D002118:Calcium