Identification of the hepatitis B virus factor that inhibits expression of the beta interferon gene

Abstract

The identity of the transacting factor encoded by the 1,828-bp BamHI DNA fragment of hepatitis B virus (HBV) that suppresses the transcription of the human beta interferon gene was investigated. Each complete and partial open reading frame (ORF) present within the 1,828-bp BamHI HBV DNA fragment was cloned into a simian virus 40 expression vector, and the resulting gene products were assayed for their ability to inhibit the activity of the regulatory DNA region that governs the expression of the beta interferon gene. Only the proteins encoded by the C ORF inhibited the activity of the beta interferon regulatory DNA region; putative proteins encoded by the partial X, P, and S ORFs present in the 1,828-bp BamHI HBV DNA fragment had no effect. A plasmid encoding only the native HBV core antigen, but not one coding for a truncated core antigen, possessed this inhibitory activity. The inhibition by the core antigen was specific for the regulatory elements of the beta interferon gene; none of a variety of viral transcriptional elements was inhibited.

RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication

“…Do these DNA-binding elements play any biological role? Transcription regulation is one possibility, and the p21.5 protamine region reportedly inhibits beta interferon gene expression (35). However, we envisage a more central role for DNA-binding activity in hepadnaviral replication, which occurs within the nucleocapsid and proceeds by reverse transcription of a pregenome RNA template, generating first single-stranded (minus-strand) DNA and then partially double-stranded DNA.…”

Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections

“…Both HBV and HCV replicate primarily in the liver, as opposed to the widespread distribution of virus in acute HIV infection, which may contribute to the difference in systemic innate activation in these infections. Additionally, HBV and HCV possess strategies for blocking type I IFN production in the cells which they infect (7,16,29,48). However, pDCs are triggered to produce IFN-␣ upon the recognition of viral components, without the need for infection.…”

A tumour necrosis factor-alpha (TNF-α) promoter polymorphism is associated with chronic hepatitis B infection

“…Infection of hepatocytes with either the hepatitis B or C virus induces the expression of TNF-a in these cells [28]. During HBV infection HBcAg can suppress the transcription of IFN-b and the HBV polymerase protein has been shown to inhibit cellular responses to IFN-a and IFN-g [29,30]. Transactivating/inhibiting factors of HBV might show differential interaction with the TNF238.2 allele and cause decreased transcription of the TNF gene.…”