Hepatitis B virus lymphotropism: emerging details and challenges

Area of Science:

• Virology
• Immunology
• Hepatology

Background:

• Hepatitis B virus (HBV) primarily targets the liver but also infects lymphatic system cells.
• HBV genetic material and proteins are detected in various extrahepatic sites, including peripheral blood mononuclear cells (PBMC).
• HBV entry into hepatocytes involves the preS1 surface protein binding to NTCP, but entry into lymphatic cells remains unclear.

Purpose of the Study:

• To investigate the presence and implications of HBV infection in extrahepatic sites, particularly PBMC.
• To understand the role of extrahepatic HBV in chronic HBV (CHB) and occult HBV infection (OBI).
• To explore HBV variants and their evolution within PBMC compartments.

Main Methods:

• Detection of HBV genomes (DNA, mRNA, cccDNA) and proteins in extrahepatic tissues like PBMC, lymph nodes, spleen, bone marrow, and cerebrospinal fluid.
• Analysis of HBV variants in PBMC from nucleos(t)ide analogue (NA) treated and untreated CHB carriers.
• Examination of HBV presence in PBMC during HBV coinfections (HCV, HIV, HDV) and pregnancy.

Main Results:

• HBV genomes are found in various PBMC subsets of chronically infected individuals.
• Unique HBV variants emerge in PBMC, indicating compartment-specific replication and evolution.
• HBV genomes are present in PBMC of individuals with HBV coinfections and during pregnancy, suggesting vertical transmission potential.

Conclusions:

• Extrahepatic HBV infection, especially in PBMC, plays a significant role in HBV pathogenesis.
• PBMC infection contributes to viral persistence, evolution of unique HBV variants, and vertical transmission.
• Further research into extrahepatic HBV reservoirs is crucial for understanding and managing HBV infection.