Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression

Abstract

Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role in the chronic carrier state in China. In our studies, the response of trophoblast cell and choriocarcinoma cell to HBV infection regarding the expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed in HTR-8/SVneo cells and JEG-3-CD133-2(+) cells after HBV infection than those in HTR-8-CD133-2(-) cells and JEG-3 cells. Our main finding is that CD133-negative cells (HTR-8-CD133-2(-) and JEG-3) are prone to HBV infection. In the last, our data indicated that the activation of Smad signaling pathway and the induction of epithelial-mesenchymal transition (EMT) in CD133-negative cells after HBV infection. In summary, our study demonstrated that CD133 is a key factor that mediated HBV infection to trophoblast cell and choriocarcinoma cell.

Keywords: HBV infection; Smad pathway; choriocarcinoma; mobility; trophoblast.

Figure 1

Detection of HBV infection in HTR-8/SVneo cell and its CD133-2 negative clone (HTR-8-CD133-2^-), and JEG-3 cell and its CD133-2 positive clone (JEG-3-CD133-2⁺). A. & B. The protein and mRNA levels of CD133-2 and HBsAg were determined by using western blot and RT-PCR.

Figure 2

The effects of HBV infection on HTR-8/SVneo, HTR-8-CD133-2^-, JEG-3 and JEG-3-CD133-2⁺ cells. A. The proliferation ratio of cells was determined by colony formation assay. B. Apoptotic ratio of cells was analyzed by using TUNEL assay. C. Gelatin zymography was used to detect the activity of MMP2. D. Wound healing assay was performed to detect the mobility of cells.

Figure 3

Western blot analysis of the Smad signaling pathway. A. Smad2, Smad3 p-Smad2, p-Smad3, E-cadherin, N-cadherin and vimentin were detected by suing western blot. B. A proposed model for signaling pathways of CD133 mediated HBV infection.