Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection.

Abstract

Several viruses are known to infect human liver and cause the hepatitis, but the interferon (IFN) response, a first-line defense against viral infection, of virus-infected hepatocytes is not clearly defined yet. We investigated innate immune system against RNA viral infection in immortalized human hepatocytes (HuS-E/2 cells), as the cells showed similar early innate immune responses to primary human hepatocytes (PHH). The low-level constitutive expression of IFN-α1 gene, but not IFN-β and IFN-λ, was observed in both PHH and HuS-E/2 cells in the absence of viral infection, suggesting a particular subtype(s) of IFN-α is constitutively produced in human hepatocytes. To examine the functional role of such IFN-α in the antiviral response, the expression profiles of innate immune-related genes were studied in the cells with the treatment of neutralization against type I IFN receptor 2 (IFNAR2) or IFN-α itself to inhibit the constitutive IFN-α signaling before and after virus infection. As the results, a clear reduction of basal level expression of IFN-inducible genes was observed in uninfected cells. When the effect of the inhibition on the cells infected with hepatitis C virus (HCV) was examined, the significant decrease of IFN stimulated gene expression and the enhancement of initial HCV replication were observed, suggesting that the steady-state production of IFN-α plays a role in amplification of antiviral responses to control the spread of RNA viral infection in human hepatocytes.

• Authors: Yoji Tsugawa, Hiroki Kato, Takashi Fujita, Kunitada Shimotohno, Makoto Hijikata
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e89869 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24587086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• DNA Primers
• Interferon-alpha

Topics

• Antibodies, Neutralizing (immunology)
• Cell Line
• DNA Primers (genetics)
• Fluorescent Antibody Technique, Indirect
• Gene Expression Profiling
• Gene Expression Regulation (immunology)
• Hepatocytes (immunology, virology)
• Humans
• Immunity, Innate (immunology)
• Immunoblotting
• Interferon-alpha (immunology)
• RNA Virus Infections (immunology)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction