Roles of pattern recognition receptors in host viral interaction during hepatitis B virus infection

Background: Hepatitis B virus (HBV) remains a major global health concern, particularly in developing countries, due to its ability to evade host immune defenses. The innate immune system serves as the first line of defense, restricting HBV and initiating adaptive immune responses for viral clearance. Both parenchymal and non-parenchymal liver cells express various pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), RIG-I-like receptors (RIG-I), melanoma differentiation-associated gene 5 (MDA-5), and nucleotide-binding oligomerization domain-like receptors (NLRs), which detect and respond to HBV. These PRRs mediate antiviral responses that suppress HBV replication and support its elimination. However, HBV has developed mechanisms to subvert these responses, notably by inactivating PRR signaling via viral proteins, enabling persistent infection. Chronic HBV infection arises from the innate immune system’s inability to control the virus in hepatocytes. Understanding PRR-mediated immunity and HBV evasion strategies is critical for developing effective immune-based therapies for both acute and chronic HBV infection.