Programmed cell death protein 1 promotes hepatitis B virus transmission through the regulation of ERK1/2-mediated trophoblasts differentiation

Abstract

Purpose The purpose of our research is to evaluate the mechanism of PD-1 in the promotion of HBV transmission. Methods HBV was used to infect two human choriocarcinoma cell line, including JEG-3, as well as BeWo. We used PCR and western blotting to detect PD-1 gene and protein expression levels in cells. Stable knockdown of the PD-1 gene in JEG-3 cells was obtained by lentiviral transfection. Trophoblast cell proliferation was evaluated using CCK8 and flow cytometry. The concentration of HBV antibody in the cell supernatant was measured by ELISA. DNA was then extracted from the cells and the copy number of the HBV virus was detected by PCR. Finally, ERK1/2 expression was detected by western blot. Results High PD-1 gene expression in HBV-infected trophoblasts and the knockdown of PD-1 gene can, respectively, improve the proliferation of HBV-infected trophoblasts and reduce viral replication in trophoblasts. In addition, PD-1 and ERK1/2 proteins were co-expressed in HBV-infected trophoblasts and inhibited the activation of ERK1/2 pathway in HBV-infected trophoblasts. ERK1/2 expression significantly increased after PD-1 knockdown. Therefore, PD-1 might be an important protein in trophoblast cells infected with HBV. Conclusions PD-1 promoted HBV transmission through regulating ERK1/2-mediated trophoblasts differentiation. Therefore, our research may provide new ideas and methods for preventing mother-to-child transmission of HBV infection during pregnancy.