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HIV infection increases HCV-induced hepatocyte apoptosis

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Author(s)
Jae Young JangRun-Xuan ShaoWenyu LinEthan WeinbergWoo Jin ChungWei Lun TsaiHong ZhaoKaku GotoLeiliang ZhangJorge Mendez-NavarroNikolaus JilgLee F. PengMark A. BrockmanRaymond T. Chung
Keimyung Author(s)
Chung, Woo Jin
Department
Dept. of Internal Medicine (내과학)
Journal Title
Journal of Hepatology
Issued Date
2011
Volume
54
Issue
4
Keyword
HCV–HIV coinfectionApoptosisTRAIL receptor
Abstract
Background & Aims: HCV related liver disease is one of the most
important complications in persons with HIV, with accelerated
fibrosis progression in coinfected persons compared to those
with HCV alone. We hypothesized that HCV–HIV coinfection
increases HCV related hepatocyte apoptosis and that HCV and
HIV influence TRAIL signaling in hepatocytes.
Methods:We analyzed the effect of HIV in JFH1-infected
Huh7.5.1 cells. Apoptosis was measured by Caspase-Glo 3/7 assay
and Western blotting for cleaved PARP. TRAIL, TRAIL receptor 1
(DR4), and 2 (DR5) mRNA and protein levels were assessed by
real-time PCR and Western blot, respectively. We also investigated
activation of caspase pathways using caspase inhibitors
and assessed expression of Bid and cytochrome C.
Results:We found increased caspase 3/7 activity and cleaved
PARP in JFH1 HCV-infected Huh7.5.1 cells in the presence of
heat-inactivated HIV, compared to Huh7.5.1 cells infected with
JFH1 or exposed to heat-inactivated HIV alone. Both DR4 and
DR5 mRNA and protein expression were increased in JFH1-
infected cells in the presence of inactivated HIV compared to
Huh7.5.1 cells infected with JFH1 or exposed to heat-inactivated
HIV alone. Pancaspase, caspase-8, and caspase-9 inhibition
blocked apoptosis induced by HCV, inactivated HIV, and HCV plus
inactivated HIV. A caspase-9 inhibitor blocked apoptosis induced
by HCV, HIV, and HCV–HIV comparably to pancaspase and caspase-
8 inhibitors.
HCV induced the activation of Bid cleavage and cytochrome C
release. The addition of HIV substantially augmented this
induction.
Conclusions: Our findings indicate that hepatocyte apoptosis is
increased in the presence of HCV and HIV compared to HCV or
HIV alone, and that this increase is mediated by DR4 and DR5
up-regulation. These results provide an additional mechanism
for the accelerated liver disease progression observed in HCV–
HIV co-infection.
Keimyung Author(s)(Kor)
정우진
Publisher
School of Medicine
Citation
Jae Young Jang et al. (2011). HIV infection increases HCV-induced hepatocyte apoptosis. Journal of Hepatology, 54(4), 612–620. doi: 10.1016/j.jhep.2010.07.042
Type
Article
ISSN
0168-8278
DOI
10.1016/j.jhep.2010.07.042
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34046
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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