HBV infection reduces pDCs’ IFN-α production in response to TLR9. HBV inhibits TLR9 signaling and transcriptional activity in pDCs and B cells, resulting in decreased TLR9 mRNA and protein levels. TLR9 mRNA and protein levels are lower in PBMC from patients with HBV-associated chronic hepatitis and HCC. Here, IFNA1 is linked to chronic hepatitis.