Imbalance in the ratio of CpG and polyG contributes to impaired interferon‐α expression

Abstract The secretion of interferon‐α (IFN‐α) is impaired during hepatitis B virus (HBV) infection. DNA sequences purified from distinct viruses, for example, HBV versus members of Herpesviridae, have been shown to differ in their IFN‐α signaling properties. The present study found that DNA from HBV inhibited, while DNA from members of Herpesviridae induced, the expression of IFN‐α. Furthermore, stimulatory cytosine‐phosphate‐guanosine (CpG) sequences derived from these DNA viruses could induce the secretion of IFN‐α, while inhibitory guanosine‐rich oligodeoxynucleoti (polyG) oligonucleotide sequences derived from these DNA viruses could inhibit CpG‐induced IFN‐α secretion. Using a computational analysis of genomic DNA sequences, the discrimination between the genomes of HBV and those of other DNA viruses that can also cause inflammation of the liver is based on different frequencies of the CpG and polyG motifs. The underrepresentation of stimulatory CpG motifs and overrepresentation of inhibitory polyG motifs were documented in HBV genomes, whereas the DNA from other viral genomes displayed the opposite trend. Moreover, it was demonstrated that HBV could suppress the activation of IFN‐α via its own DNA through the high proportion of polyG motifs. To our knowledge, this is the first demonstration of a specific role for polyG motifs in the inhibition of the IFN‐α response following DNA virus infection.