O papel não-estrutural da proteína do capsídeo do vírus da dengue

Biochemical and Biophysical Research Communications 418 (2012) 622–627

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Dengue virus utilizes calcium modulating cyclophilin-binding ligand to subvert apoptosis
Jianling Li a,1, Rongjie Huang a,1, Weiyong Liao b, Zhaoni Chen c, Shijun Zhang c,⇑, Renbin Huang c,⇑ a Department of Internal Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China Department of Physiology, Guilin Medical University, Guilin, Guangxi 541004, China c Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi 530021, China b a r t i c l e

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a b s t r a c t
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 36 h 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 36 h 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 36 h