E2 of hepatitis C virus inhibits apoptosis.
Hepatitis C virus (HCV) is the major causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, and can be involved in very long chronic infections up to 30 years or more. Therefore, it has been speculated that HCV possesses mechanisms capable of modulating host defense systems such as innate and adaptive immunity. To investigate this virus-host interaction, we generated HCV replicons containing various HCV structural proteins and then analyzed the sensitivity of replicon-containing cells to the apoptosis-inducing agent, TRAIL. TRAIL-induced apoptosis was monitored by cleavage of procaspase-3 and procaspase-9 as well as that of their substrate poly(ADP-ribose) polymerase. TRAIL-induced apoptosis was inhibited in cells expressing HCV E2. Moreover, expression of HCV E2 enhanced the colony forming efficiency of replicon-containing cells by 25-fold. Blockage of apoptosis by E2 seems to be related to inhibition of TRAIL-induced cytochrome c release from the mitochondria. Based on these results, we propose that E2 augments persistent HCV infection by blocking host-induced apoptosis of infected cells.
Lee
Song Hee
SH
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
Kim
Yoon Ki
YK
Kim
Chon Saeng
CS
Seol
Su Kyoung
SK
Kim
Joonhyun
J
Cho
Sungchan
S
Song
Young Lan
YL
Bartenschlager
Ralf
R
Jang
Sung Key
SK
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006526:Hepatitis C / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D012093:Replicon / Q000235:genetics; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014759:Viral Envelope Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus; D045304:Cytochromes c