Innate host response in primary human hepatocytes with hepatitis C virus infection

Darong Yang, Nianli Liu, Chaohui Zuo, Shoahua Lei, Xinjiao Wu, Fei Zhou, Chen Liu, Haizhen Zhu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background and Aim: The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection. Methods: An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined. Results: Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes. Conclusion: Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection.

Original languageEnglish (US)
Article numbere27552
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 8 2011

Fingerprint

Hepatitis C virus
Virus Diseases
Viruses
Hepacivirus
hepatocytes
Hepatocytes
infection
apoptosis
Apoptosis
Viral RNA
viruses
Antiviral Agents
cells
Hepatovirus
hepatitis A
viral proteins
Viral Proteins
interferons
Proteins
Flow cytometry

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Innate host response in primary human hepatocytes with hepatitis C virus infection. / Yang, Darong; Liu, Nianli; Zuo, Chaohui; Lei, Shoahua; Wu, Xinjiao; Zhou, Fei; Liu, Chen; Zhu, Haizhen.

In: PloS one, Vol. 6, No. 11, e27552, 08.11.2011.

Research output: Contribution to journalArticle

Yang, D, Liu, N, Zuo, C, Lei, S, Wu, X, Zhou, F, Liu, C & Zhu, H 2011, 'Innate host response in primary human hepatocytes with hepatitis C virus infection', PloS one, vol. 6, no. 11, e27552. https://doi.org/10.1371/journal.pone.0027552
Yang, Darong ; Liu, Nianli ; Zuo, Chaohui ; Lei, Shoahua ; Wu, Xinjiao ; Zhou, Fei ; Liu, Chen ; Zhu, Haizhen. / Innate host response in primary human hepatocytes with hepatitis C virus infection. In: PloS one. 2011 ; Vol. 6, No. 11.
@article{03535aa7f7aa4685b5dea932e4558bcc,
title = "Innate host response in primary human hepatocytes with hepatitis C virus infection",
abstract = "Background and Aim: The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection. Methods: An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined. Results: Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes. Conclusion: Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection.",
author = "Darong Yang and Nianli Liu and Chaohui Zuo and Shoahua Lei and Xinjiao Wu and Fei Zhou and Chen Liu and Haizhen Zhu",
year = "2011",
month = "11",
day = "8",
doi = "10.1371/journal.pone.0027552",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Innate host response in primary human hepatocytes with hepatitis C virus infection

AU - Yang, Darong

AU - Liu, Nianli

AU - Zuo, Chaohui

AU - Lei, Shoahua

AU - Wu, Xinjiao

AU - Zhou, Fei

AU - Liu, Chen

AU - Zhu, Haizhen

PY - 2011/11/8

Y1 - 2011/11/8

N2 - Background and Aim: The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection. Methods: An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined. Results: Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes. Conclusion: Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection.

AB - Background and Aim: The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection. Methods: An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined. Results: Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes. Conclusion: Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection.

UR - http://www.scopus.com/inward/record.url?scp=80555154422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80555154422&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0027552

DO - 10.1371/journal.pone.0027552

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e27552

ER -