Inhibition of hepatitis C virus infection by interferon-gamma through downregulating claudin-1.
Hepatitis C virus (HCV) is a serious global health threat and current medical treatment options are limited. Interferon (IFN)-gamma is an important proinflammatory cytokine with antiviral activity. However, the mechanism of IFN-gamma in anti-HCV infection remains unclear. In this study, we investigated the role of IFN-gamma on HCV infection of polarized Caco-2 cells using cell culture-derived HCV (HCVcc). We found that downregulation of claudin-1 (CLDN1) induced by IFN-gamma resulted in disruption of barrier function as demonstrated by measurement of transepithelial electrical resistance and dextran permeability. Further, results from confocal microscopy and Western blot analysis showed that in addition to the reduction of CLDN1 expression, IFN-gamma treatment also led to significant changes in the distribution of CLDN1, CD81, and scavenger receptor class B type I. Moreover, infection assays revealed that IFN-gamma-treated cells showed decreased susceptibility to HCVcc infection. These results suggest a novel mechanism that IFN-gamma may inhibit HCV infection by regulating CLDN1 expression and distribution of HCV receptors.
Wei
Xin
X
Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Jia
Zhan-Sheng
ZS
Lian
Jian-Qi
JQ
Zhang
Ye
Y
Li
Jun
J
Ma
Li
L
Ye
Ling
L
Wang
Jiu-Ping
JP
Pan
Lei
L
Wang
Ping-Zhong
PZ
Bai
Xue-Fan
XF
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D062445:Claudin-1; D015536:Down-Regulation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D060225:Tetraspanin 28; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D007371:Interferon-gamma