Human Herpesvirus 6 Activates NF-κB Signalling and CD163-Positive Macrophage Recruitment in Alcohol-Induced Hepatic Injury.

Abstract

Human herpesvirus 6 (HHV-6) establishes lifelong latency in immune cells and may contribute to the progression of ethanol-induced liver injury. To elucidate the contribution of HHV-6 to alcohol-induced hepatic injury, this study evaluated HHV-6 protein expression, NF-κB signalling, and CD163-positive macrophage recruitment in liver samples from control subjects, young individuals with recent alcohol exposure, and individuals with long-term chronic alcohol use. Liver lobules displaying HHV-6 positivity were more frequent in alcohol users (64% in young and 72% in chronic users) compared to controls (48%). CD163-positive macrophage counts were higher in both young and chronic alcohol users compared to controls, with the greatest increase in HHV-6-positive chronic users. NF-κB expression intensity was elevated in alcohol users (p < 0.005), and further increased in HHV-6-positive samples (p = 0.02). These findings indicate an association between HHV-6 persistence, NF-κB pathway activation, and CD163-positive macrophage-driven inflammatory responses in liver tissue under conditions of chronic alcohol use. Further research is warranted to uncover the mechanisms underlying the interaction between HHV-6 and ethanol in liver injury.