Open Access

HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts

  • Authors:
    • Yayun Lin
    • Yan Liu
    • Dongping Xu
    • Fanfan Guo
    • Wentao Zhang
    • Yidan Zhang
    • Guiqin Bai
  • View Affiliations

  • Published online on: August 24, 2021     https://doi.org/10.3892/etm.2021.10645
  • Article Number: 1211
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatitis B virus (HBV) infection is a global epidemic. The main transmission route of chronic HBV infection is from mother to child, yet the mechanisms underlying HBV intrauterine infection remain unclear. In the present study, the effect and the mechanism underlying hepatitis B virus X antigen (HBxAg) on HBV replication and EGFR activation in trophoblasts was investigated. Serum samples from pregnant women with HBV infection were used to infect trophoblasts and HBxAg expression was detected using ELISA. HBV plasmids carrying either full length hepatitis B virus X (HBx) or HBx with a deletion mutation (ΔHBx) were transfected into trophoblasts and expression levels of HBV DNA, hepatitis B e‑antigen and pregenomic (pg)RNA, and structural maintenance of chromosomes (Smc) 5/6 were assessed. The association between HBx and EGFR promoters was characterized using a luciferase reporter assay and EGFR/PI3K/phosphorylated (p)‑AKT expression and apoptosis rate were also monitored. The results of the present study indicated that HBxAg expression increased with the increasing titre of HBV DNA (P<0.05). Compared with the wild‑type group, the amount of HBV DNA in the supernatant and cells was significantly reduced (P<0.05) in the ΔHBx group and the intracellular HBeAg and pgRNA levels were also significantly decreased (P<0.05). In addition, Smc5/6 expression was also significantly decreased (P<0.05) when the intracellular HBx protein was expressed compared with mock‑transfected cells. Co‑transfection of HBx and EGFR promoter plasmids in JEG‑3 and HTR‑8 cells significantly elevated EGFR promoter driven luciferase expression relative to the control group (P<0.01). In EGFR overexpressing cells, the expression of PI3K/p‑AKT was significantly increased, whereas the apoptosis rate was significantly decreased (P<0.05). These results were reversed in the EGFR‑knockdown group. In conclusion, the present study demonstrated that HBx promotes HBV replication in trophoblasts via downregulation of Smc5/6, activates the EGFR promoter and inhibits trophoblast apoptosis via the PI3K/p‑AKT downstream signalling pathway, thereby increasing the risk of HBV intrauterine infection.
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November-2021
Volume 22 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Lin Y, Liu Y, Xu D, Guo F, Zhang W, Zhang Y and Bai G: HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts. Exp Ther Med 22: 1211, 2021
APA
Lin, Y., Liu, Y., Xu, D., Guo, F., Zhang, W., Zhang, Y., & Bai, G. (2021). HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts. Experimental and Therapeutic Medicine, 22, 1211. https://doi.org/10.3892/etm.2021.10645
MLA
Lin, Y., Liu, Y., Xu, D., Guo, F., Zhang, W., Zhang, Y., Bai, G."HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts". Experimental and Therapeutic Medicine 22.5 (2021): 1211.
Chicago
Lin, Y., Liu, Y., Xu, D., Guo, F., Zhang, W., Zhang, Y., Bai, G."HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1211. https://doi.org/10.3892/etm.2021.10645