Negative regulation of hepatitis B virus gene expression and replication by oxidative stress

We present data demonstrating that hydrogen peroxide markedly decreases release of progeny hepatitis B virus particles in cultured cells. The presence of reduced glutathione prevents this effect. Hydrogen peroxide also decreases secretion of the hepatitis B virus surface and e antigens, with a concomitant decrease in the steady-state levels of the corresponding viral transcripts. This effect is specific to viral gene expression, since hydrogen peroxide at the concentration used does not have any significant effect on the overall pattern of host cell protein synthesis nor on the secretion of growth hormone from a co-transfected plasmid. Since hepatitis B virus can cause acute and chronic hepatitis and since inflammatory cells release significant amounts of reactive oxygen species, including hydrogen peroxide, this phenomenon may be of pathophysiological importance in the viral life cycle.