Hepatitis B virus (HBV) can be vertically transmitted from mother to babies. Unlike exposure at adulthood, immunological consequences of such exposure to HBV in newborns is "tolerance" to chronic HBV infection.
Ordinarily mice are not naturally infected with HBV. New paper in Immunity reported development of mouse model to study immunology of vertical transmission of HBV.
This model is a combination of two independent processes: 1st, use of HBV transgenic mice and 2nd, hydrodynamic injection of plasmid that contained 1.3-mer HBV genomic DNA. Initially, the authors showed mice born to HBV Tg females (referred here as TGD mouse), but not controls, developed "chronic HBV infection" when exposed to HBV plasmid.
Analysis of HBV-specific CD8 T cells from HBV-DNA injected TGD mice liver showed up-regulation of checkpoint inhibitor PD-1 on T cells.
Treatment of TGD mice with anti-PDL1 antibody enabled them to control HBV-DNA infection.
Moreover, the authors found that clodronate-liposome depletion of macrophages from TGD mice also enabled them to control HBV-DNA infection.
Finally, the authors found that HBVeAg played important role in viral persistence and tolerance by observing that (a) mice born to HBV-mut Tg females (HBV lacking eAg) do not develop persistent HVB-DNA infection, and (b) TGD mice exposed to HBV-DNA lacking eAg also were able to eliminate virus.
In summary, this study suggests that HBVeAg controls newborn's tolerance to HBV via inhibitory PD-L1 signaling.
Few additional thoughts: first, the authors reported that after HBV-DNA injection, around 15% of liver macrophages, called Kupffer cells, expressed viral antigen. However, they also found that >75% of Kupffer cells expressed PD-L1 upon HBV-DNA injection. Second, since HBV virus from HBV Tg pregnant females cannot directly infect newborns, it is not clear how HBVeAg is able to modulate macrophages and tolerize newborn's CD8 T cells (the authors also acknowledged this inconsistency).
David Usharauli
Finally, the authors found that HBVeAg played important role in viral persistence and tolerance by observing that (a) mice born to HBV-mut Tg females (HBV lacking eAg) do not develop persistent HVB-DNA infection, and (b) TGD mice exposed to HBV-DNA lacking eAg also were able to eliminate virus.
In summary, this study suggests that HBVeAg controls newborn's tolerance to HBV via inhibitory PD-L1 signaling.
Few additional thoughts: first, the authors reported that after HBV-DNA injection, around 15% of liver macrophages, called Kupffer cells, expressed viral antigen. However, they also found that >75% of Kupffer cells expressed PD-L1 upon HBV-DNA injection. Second, since HBV virus from HBV Tg pregnant females cannot directly infect newborns, it is not clear how HBVeAg is able to modulate macrophages and tolerize newborn's CD8 T cells (the authors also acknowledged this inconsistency).
David Usharauli
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