Influence of HBx in cellular pathways and process
| Pathway and process | Effect | References |
|---|---|---|
| MAPK signaling pathway | Enhancement of MAPK activation leading to cell proliferation, prevention of apoptosis, and gene expression regulation. | [19, 20] |
| PI3K/AKT signaling pathway | Stimulation of the PI3K/AKT signaling pathway, resulting in apoptosis suppression, increased cell proliferation that might disrupt cellular communication, and boost its survival within host hepatocytes. | [21, 22] |
| JAK-STAT signaling pathway | Disruption of JAK-STAT signaling system, resulting in immunological suppression, increased cell survival, and proliferation. Interference with the JAK-STAT pathway leads to HBV infection persistence. | [18] |
| NF-κB signaling pathway | Activation of NF-κB signaling pathway, resulting in enhanced inflammation, immunological regulation, cell survival, and proliferation. | [23, 24] |
| Oxidative stress | Imbalance between ROS production and antioxidant defense mechanisms within hepatocytes, leading to increased oxidative stress. This oxidative stress contributes to DNA damage, genomic instability, inflammation, and cell survival pathways that collectively promote liver damage. | [25, 26] |
| Apoptosis and DNA repair mechanism | Inhibition of apoptosis and DNA repair mechanisms in a way that promotes cell survival, inhibits programmed cell death, and can contribute to genomic instability. | [27, 28] |
| Autophagy mechanism | The effect of HBx-induced autophagy (activation of P13K/AKT-mTOR, and interference with autophagic flow) may help infected hepatocytes survive by eliminating damaged cellular components and promoting viral replication. | [29, 30] |
| Epigenetic modification | Induction of epigenetic modifications such as DNA methylation, histone alterations, remodeling of chromatin, and various miRNAs that all together affect gene expression patterns and cellular responses. | [31–33] |
mTOR: mammalian target of rapamycin; miRNAs: microRNAs
