NF-κB activation induced by hepatitis A virus and Newcastle disease virus occurs by different pathways depending on the structural pattern of viral nucleic acids.

NF-κB is activated by hepatitis B virus and hepatitis C virus and is assumed to contribute to viral persistence, leading to the development of hepatocellular cancer by inhibition of apoptosis mediated by cytotoxic T cells. Whether hepatitis A virus (HAV), which does not cause chronic infection, activates NF-κB is a topic of controversy. Here, we confirm that HAV activates NF-κB and show that HAV enhances the activation of NF-κB by poly(I-C), but it inhibits the activation of NF-κB by Newcastle disease virus (NDV), a paramyxovirus.

Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon.

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of double-stranded RNA (dsRNA)-induced beta interferon (IFN-beta) gene expression. In this report, we show that this is due to an interaction of HAV with the intracellular dsRNA-induced retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway upstream of the kinases responsible for interferon regulatory factor 3 (IRF-3) phosphorylation (TBK1 and IKKepsilon). In consequence, IRF-3 is not activated for nuclear translocation and gene induction.

Hepatitis A virus inhibits cellular antiviral defense mechanisms induced by double-stranded RNA.

The consequences of a hepatitis A virus (HAV) infection on cell-based antiviral responses and the interactions between virus and host cells resulting in persistent infections are poorly understood. In this report, we show that HAV does inhibit double-stranded (dsRNA)-induced beta interferon (IFN-beta) gene expression by influencing the IFN-beta enhanceosome, as well as dsRNA-induced apoptosis, which suggests that both effects may be connected by shared viral and/or cellular factors. This ability of HAV, which preserves the sites of virus production for a longer time, may allow the virus to establish an infection and may be the presupposition for setting up persistent infections.