Acta Virologica Vol.49, p.183-193, 2005
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Title: EFFECT OF CORDYCEPIN ON HANTAAN VIRUS 76-118 INFECTION OF
PRIMARY HUMAN EMBRYONIC PULMONARY FIBROBLASTS –
CHARACTERIZATION OF APOPTOTIC EFFECTS |
Author: F.-L. XU, Y.-L. LEE, W.-Y. TSAI, S.-J. LIN, Z.-Q. YANG, C.-C. YANG, H.-Y. LIU, L. CHENG, H. XIAO, L. WEN |
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Abstract: The cDNA microarray technique was used to study gene epression in human embryonic
pulmonary fibroblasts (HEPF) infected with Hantaan virus (HTNV) under the influence of cordycepin (Cor),
an inhibitor of post-transcriptional pre-mRNA polyadenylation. Four apoptotic genes, the insulin-like growth
factor binding protein 1, NFkB inhibitor alpha, caspase-3 and NFkB1 were up-regulated in both infected and
uninfected Cor-treated cells and two cell cycle-associated genes, CDC-like kinase and beta-induced transforming
growth factor were up-regulated in Cor-untreated cells but down-regulated in Cor-treated cells. Cell morphology
examination, quantitative RT-PCR, and immunofluorescence (IF) test suggested that following the Cor treatment
the HTNV infection took place, but late viral gene expression was slightly reduced. Three parameters, namely
caspase-3 activity, annexin V binding, and cell cycle were used to detect apoptosis. The results suggested that
the induction of apoptosis in HEPF by HTNV started at 6 hrs post infection (p.i.). Following the Cor treatment,
however, the caspase-3 activity began to increase at 24 hrs p.i. Thus it is suggested that inhibition of de novo
late viral protein synthesis by Cor changes the apoptosis pathway and cell cycle by delaying caspase-3 gene
expression and by up/down-regulating of expression of other apoptotic and cell cycle-associated genes. This
implicates that HTNV can induce apoptosis in HEPF even without de novo viral protein synthesis and with
a reduced and slowed viral maturation.
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Keywords: annexin V; apoptosis; caspase-3; cordycepin; flow cytometry; Hantaan virus; microarray; phosphatidylserine; RT-PCR |
Year: 2005, Volume: 49, Issue: |
Page From: 183, Page To: 193 |
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