Roles of Toll-like Receptor 3 in Intrauterine Transmission of Hepatitis B Virus in Mothers with High Viral Load

Backgrounds: Despite passive and active immunization, perinatal mother-to-infant transmission (MTIT) of hepatitis B virus (HBV) still occurs in women with high levels of viremia. Thus, understanding the mechanisms of MTIT is essential to prevent MTIT. The aims of this study were to clarify the roles of toll-like receptor 3 (TLR3) in the prevention of hepatitis B transmission in mothers with a high viral load. Methods: Placental samples were collected from 87 HBV-positive pregnant women and 25 normal pregnant women. Choriocarcinoma JEG-3 cell lines were exposed to different HBV viral loads to mimic the trophoblast barrier affected by HBV in the placenta. The mRNA and protein expression levels of TLR3 were analyzed by qRT-PCR and western blotting assays in placenta and JEG-3 cells, respectively. Results: In terms of mRNA and protein expression, the expression of TLR3 in the placenta among the control, low viral load, medium viral load and high viral load groups were significantly different, showing significant upregulation in the medium load and high load groups compared with the control; TLR3 expression in the placenta of the HBeAg-positive group was higher than that in the HBeAg-negative group, and TLR3 expression in the placenta of the infant-infected group was lower than that of the infant-noninfected group. Expression of TLR3 was gradually increased in JEG-3 cells exposed to low HBV viral loads or with shortterm HBV exposure and was decreased in JEG-3 cells exposed to high HBV viral loads or with longterm HBV exposure. Conclusions: TLR3 contribute to HBV intrauterine infection in mothers with a high viral load and, importantly, prevents mother-to-infant transmission.