Abstract
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.
Highlights
Chronic hepatitis B virus (HBV) infection leads to chronic hepatitis, liver failure, cirrhosis and hepatocellular carcinoma [1]
The results have shown that TLR7 and TLR8 on trophoblastic cells inhibit HBV translocation across trophoblasts, indicating an important role in the prevention of intrauterine HBV transmission: expression of TLR7 was significantly higher in HBV-positive women whose infants were noninfected than HBV-positive women whose infants were infected, and TLR8 expression was significantly higher in the noninfected group than in the control . [22] HBV can inhibit the secretion of TLR9 in HBV-positive women to some extent, but HBeAg can stimulate the secretion of TLR9, and with the increased severity of intrauterine transmission of HBV, the level of TLR9 expression in HBV-positive women is increased
Acknowledgement we observed that the expression of Toll-like receptors (TLR) was differently regulated in the placentas of pregnant women with CHB; the mRNA and protein levels of toll-like receptor 3 (TLR3) were significantly upregulated in the medium load viral group (103≤ HBV loads
Summary
Chronic hepatitis B virus (HBV) infection leads to chronic hepatitis, liver failure, cirrhosis and hepatocellular carcinoma [1]. Mother-to-infant transmission (MTIT) is one of the main mechanisms of hepatitis B virus (HBV) transmission in pregnant mothers with chronic HBV infection . MTIT of HBV primarily occurs by intrauterine transmission, accounting for 13-44% of HBV transmission [6]. A growing number of studies compared mothers with high HBV viral load (ranged from 105-108copies/mL) or with HBeAg positivity to those with low HBV DNA levels or HBeAg negativity during gestation. They found that intrauterine transmission was more likely to occur during gestation in people with high viral load or HBeAg positivity, leading to transmitting HBV to their babies . They found that intrauterine transmission was more likely to occur during gestation in people with high viral load or HBeAg positivity, leading to transmitting HBV to their babies . [7,8,9,10,11] Reduction of HBV DNA levels below 106 copies/mL reduced the risk by approximately 30% . [12] Ac-
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