Abstract
Background/AimThe hepatitis B virus (HBV) infection is accompanied by the induction of oxidative stress, especially mediated by HBV X protein (HBx). Oxidative stress has been implicated in a series of pathological states, such as DNA damage, cell survival and apoptosis. However, the host factor by which cells protect themselves under this oxidative stress is poorly understood.Methodology/Principal FindingsIn this study, we first confirmed that HBV infection significantly induced oxidative stress. Moreover, viral protein HBx plays a major role in the oxidative stress induced by HBV. Importantly, we found that mitochondrial protein SIRT3 overexpression could decrease reactive oxygen species (ROS) induced by HBx while SIRT3 knockdown increased HBx-induced ROS. Importantly, SIRT3 overexpression abolished oxidative damage of HBx-expressing cells as evidenced by γH2AX and AP sites measurements. In contrast, SIRT3 knockdown promoted HBx-induced oxidative damage. In addition, we also observed that oxidant H2O2 markedly promoted HBV replication while the antioxidant N-acetyl-L-cysteine (NAC) inhibited HBV replication. Significantly, SIRT3 overexpression inhibited HBV replication by reducing cellular ROS level.Conclusions/SignificanceCollectively, these data suggest HBx expression induces oxidative stress, which promotes cellular oxidative damage and viral replication during HBV pathogenesis. Mitochondrial protein SIRT3 protected HBx expressing-cells from oxidative damage and inhibited HBV replication possibly by decreased cellular ROS level. These studies shed new light on the physiological significance of SIRT3 on HBx-induced oxidative stress, which can contribute to the liver pathogenesis.
Highlights
Human hepatitis B virus (HBV) infection is a public health problem which affects nearly 350 million people worldwide [1]
We found that the HBV replication induced cellular reactive oxygen species (ROS) level based on different cell models, which suggests that HBV replication induces oxidative stress
Among the proteins encoded by the HBV genome, HBV X protein (HBx) is a key viral protein that plays an important role in oxidative stress
Summary
Human HBV infection is a public health problem which affects nearly 350 million people worldwide [1]. Among SIRT1-7, SIRT3 is a major mitochondrial deacetylase that targets no less than 20% of the proteome located in mitochondrial [2] It deacetylates and activates several mitochondrial proteins that involved in mitochondrial oxidative metabolism and energy production, such as subunits of complex II and V of the electron transport chain [3,4,5,6]. The SIRT3-catalyzed deacetylation of 8-oxoguanine-DNA glycosylase 1 (OGG1) protects mitochondrial DNA from oxidative damage and prevents apoptotic cell death under oxidative stress [10]. These studies highlight the significance of SIRT3 to protect cells from oxidative damage
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