Is the function of the HBeAg really unknown?

Abstract

The immune response to the hepatitis B virus (HBV) vaccine in newborns of hepatitis B e antigen (HBeAg)-positive or HBeAg-negative mothers is the subject of Huang et al. The authors report no correlation between the HBeAg status of the mothers/cord blood and the newborns immune response to the vaccine, but, unfortunately, draw unfounded conclusions regarding the tolerogenic potential of in utero exposure to HBeAg. In this reply, I address the possible influence of in utero exposure to the HBeAg, and briefly review other characteristics of the HBeAg, that may promote HBV chronicity. I argue that the function of HBeAg should no longer be considered "unknown" and that immunotolerance/immunomodulation represent the dominant functions of the HBeAg in viral-host interactions.

Keywords: HBV vaccine; HBeAg; Hepatitis B virus; chronicity; immune tolerance.

Figure 1.

The dual roles of HBeAg. (a). Serum HBeAg inhibits spontaneous IgG anti-HBc Ab production in vivo in a HBc-Tg lineage that is not tolerant to the HBcAg. IgG anti-HBc Ab was measured in the serum of six HBc-Tg and six HBc × HBe double-Tg (dbl-Tg) mice on a genetic background of a HBe/HBcAg-specific, CD4+ TCR-Tg strain. Adapted from Ref. [6]. (b). Liver injury persists longer when the HBcAg and HBeAg are co-expressed in the liver. To mimic the period when HBeAg-specific tolerance is subsiding, activated polyclonal HBc/HBeAg-specific CTL cells were transferred into HBc-Tg or HBc × HBe dbl-Tg mice recipients and serum ALT levels were measured as a marker of liver injury. Adapted from Ref. [33].