Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition

Area of Science:

• Immunology
• Virology
• Metabolism

Background:

• Innate immunity and glucose metabolism are interconnected.
• The interaction between these systems during Hepatitis B Virus (HBV) infection is not well understood.
• Understanding these mechanisms is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the interplay between glucose metabolism and innate immunity during HBV infection.
• To elucidate the mechanisms by which HBV influences immune responses.
• To identify potential therapeutic targets for HBV treatment.

Main Methods:

• In vitro and in vivo experiments were conducted.
• Pharmacological and genetic approaches were employed.
• Key proteins such as hexokinase (HK) and MAVS were analyzed.

Main Results:

• HBV activates glycolysis, leading to the suppression of retinoic acid-inducible gene I (RIG-I)-induced interferon production.
• HBV forms a ternary complex with hexokinase (HK) to sequester MAVS from RIG-I.
• Lactate dehydrogenase-A-dependent lactate production by HBV suppresses RIG-I-like receptor (RLR) signaling.
• Lactate directly binds MAVS, inhibiting its aggregation and mitochondrial localization.
• Hexokinase 2 (HK2) and glycolysis-derived lactate are critical for HBV immune escape.

Conclusions:

• HBV utilizes glucose metabolism to evade innate immune responses.
• Energy metabolism plays a significant role in regulating innate immunity during HBV infection.
• Targeting HK2 and lactate production may represent a novel strategy for controlling HBV infection.