Studies on interaction between host thioredoxin-interacting protein and hepatitis C virus infection

Abstract

Objective To explore the relationship between host cell thioredoxin-interacting protein (TXNIP) and hepatitis C virus (HCV) replication, as well as the mechanism of how TXNIP promotes HCV replication. Methods The transcriptome shift of Huh7 cells after cell cultrued HCV (HCVcc) infection was analyzed by using Glue Grant Human Transcriptome Microarray. The differential expression of TXNIP was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and high-throughput sequencing. The effect of TXNIP on HCV infection was tested by TXNIP overexpression and TXNIP knockdown. Results Transcriptome array demonstrated a 3.7 times fold upregulation of TXNIP mRNA in HCVcc infected Huh7 cell higher than those without HCVcc infection, which was further verified by high-throughput deep sequencing. The TXNIP mRNA level was significantly up-regulated at 36 h and 60 h post HCV infection (t=24.90 and 8.27, respectively, both P<0.01). In cell level analysis, knockdown of TXNIP by small interfering RNA (siRNA) could reduce HCV infection, while TXNIP overexpression could enhance HCV replication. Infection with HCVcc could increase the expression of TXNIP in Huh7 but not in Huh7.5.1 cells, and interferons α, β, and γ treatment could up-regulate TXNIP expressions in both cell lines. Conclusions HCV infection induces host cell TXNIP expression, and upregulated TXNIP enhances HCV replication. Host cell TXNIP plays an important role in HCV replication, infection and immune escape. Key words: Hepacivirus; Thioredoxin-interacting protein; Interferons