Interferon-lambda in the immune response to hepatitis B virus and hepatitis C virus

Abstract

Approximately 500 million people worldwide are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV), and are therefore at an increased risk for developing fatal liver diseases such as cirrhosis and hepatocellular carcinoma. The intracellular antiviral responses induced by interferon (IFN)-alpha/-beta and/or IFN-gamma play critical roles in the pathogenesis of HBV and HCV infection, and the function of IFN-lambda in the host immune response to these viruses is beginning to be revealed. A better understanding of how IFN-lambda influences HBV or HCV persistence is not only important for understanding the mechanisms of chronic virus infection, but also may lead to new approaches for improved antiviral therapies.

FIG. 1.

Interferon (IFN)-λ sensitivity and production in primary brain cells. (A) Induction of the representative IFN-stimulated genes MxA and IFI27 24 h after stimulation of primary astrocytes (Astro), choroids plexus (CP) endothelial (Endo) or epithelial (Epi) cells, neurons, or mixed brain cells with 2 ng (500 U)/mL IFN-α2a or 250 ng/mL IFN-λ1. Also shown is expression of MxA and IFI27 in primary hepatocytes (Hepat) under identical stimulation conditions. Gene expression is displayed as fold induction relative to untreated cells and normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) measured by quantitative reverse-transcription PCR (RT-qPCR), and error bars indicate relative quantification maximum and minimum values. (B) Expression of IFN-λ1 or IFN-λ2/3 mRNA 6 h after infection with vesicular stomatitis virus at the indicated MOI. Gene expression is displayed as fold induction relative to uninfected cells normalized to GAPDH, as measured by RT-qPCR.

FIG. 2.

IL-28Rα and IL-10Rβ expression in liver and brain cells. Expression of (A) IL-28Rα and (B) IL-10Rβ mRNA in the hepatocellular carcinoma cell lines Huh-7 and HepG2, the glioblastoma cell lines U87 and U373, and primary hepatocytes (Hepat), mixed brain cells, neurons, and astrocytes (Astro). Expression levels were measured by RT-qPCR, and are displayed as relative to the lung epithelial cell line A549. Data are displayed as the mean of 3 replicate measurements, and error bars indicate standard error of the mean.