HBV has evolved a unique life cycle that results in the production of enormous viral loads as well

 

　　as antigen loads during active replication without actually killing the infected cell directly, and the liver damage in chronic hepatitis B (CHB) is the result of the host’s cellular immune response to HBVinfected hepatocytes as part of the “immune clearance” phase of the disease. This afternoon, Professor Stephen Locarnini from the Victorian Infectious Disease Reference Laboratory, North Melbourne, Australia will give a lecture on the topic of innate immunity in hepatitis B.

 

　　HBV has developed a number of strategies to ensure its persistence in the infected host, including the production of excess HBsAg and the expression of HBeAg. The HBeAg is a powerful modulator of the innate immune response by downregulation of Toll-like receptors (TLR), allowing viral persistence within the host. The N-terminal 10 amino acids of the HBeAg (precore protein) contains a Toll/interleukin-1 receptor (TIR) motif, blocking not only TLR-2, but also TLR-3, Mal, TRIF and TRAM signaling, thereby inhibiting both NF-κβ and interferon (IFN)-β activation. Likewise, HBsAg inhibits TLR-9 mediated activation and IFN-α production in plasmacytoid dendritic cells. Thus, HBV could effectively suppress type I IFN responses in hepatocytes.

 

　　The cccDNA is found only in infected hepatocytes and as a minichromosome. The HBcAg

 

　　protein is a key structural component and positive regulator of the minichromosome. Both IFN-α and lymphotoxin β-agonists can activate APOBEC 3A/3B and results in selective (APOBEC-HBV core interaction) HBV cccDNA degradation following cytidine deamination.

 

　　Because HBV uses reverse transcription to copy its genome, mutant viral genomes emerge frequently. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antiviral drugs), readily select out these escape variants. Therefore, further studies are needed to identify the pathogenesis and clinical sequelae arising from the selection of these particular mutants as well as to the “wild-type” HBV infections.

 

Symposium 6:Novel Therapeutic Strategies for HBV - "Innate Immunity in Hepatitis B"

14:10 - 14:30

Room 1BC