In humans, most HBV infection in the adult resolves after the acute disease, however, around ninety percent of the infection in neonates and childhood leads to chronic HBV persistence. Until today, causes for the age-dependent infection outcome of HBV are still unclear. By using hydrodynamic injection of replication-competent HBV DNA plasmid, we established a mouse model of in vivo HBV transfection in which HBV persistence was generated in young C57BL/6 mice of 4-6 w/o, but not in mice older than 10 w/o. In this system, we found that there was higher hepatic IFN-alpha/beta expression in the young mice after HBV transfection compared to adult mice. We speculate that differential IFN-alpha/beta immune regulation during early HBV infection leads to the age-dependent HBV persistence outcome. To address this, the adult mice were overexpressed with IFN-beta in the liver. HBV persistence rate of these mice was increased compared to controls. In addition, blockage of IFN-alpha/beta signaling in the young mice accelerated HBV clearance. The young mice expressed more IFN-alpha/beta-associated immune suppressor genes, Axl/Twist, after HBV transfection than the adult mice, suggesting that type-I IFN executed active immune suppression towards HBV immunity in the young mice. Our findings suggest a role for IFN-alpha/beta in suppressing effective anti-HBV immunity in the young mice and shed light on our understanding of the age-dependent immune function during early HBV infection.
- Copyright © 2011 by The American Association of Immunologists, Inc.