Intrauterine Infection and Mother-to-Child Transmission of Hepatitis B Virus: Route and Molecular Mechanism

Abstract

In high prevalence settings, mother-to-child transmission is responsible for more than 50% of chronic Hepatitis B Virus (HBV) infections with 1–9% of newborns of HBV-carrying mothers acquiring HBV in early life. Little is known about the routes and cellular mechanisms by which HBV intrauterine transmission occurs. Clinical studies indicate that placental trophoblasts can be infected with HBV. In vitro studies using primary trophoblast and cell lines support this hypothesis. Several cellular parameters, including the differentiation state of the trophoblasts, cytokine secretion, and the surface molecules involved in virus entry, may influence the receptivity of trophoblastic cells to HBV. In HBV-infected trophoblastic cells, a reduction of apoptosis and increased production of antiviral cytokines has been observed, presumably via an HBx antigen-Akt or TLRs-MyD88-NF-kB pathway. Trophoblast HBV infection occurrence involves complex pathological processes with little currently known of the related mechanisms within infected cells. Whilst much focus has been on the placental routes of infection, through trophoblasts in particular, other routes have also been suggested. In this article, we review the models for HBV mother-to-child transmission and discuss the possible mechanisms of HBV intrauterine transmission with particular emphasis upon the involvement of placental trophoblast infection.

High Seroprevalence of Hepatitis B and C Virus Infections among Pregnant Women Attending Antenatal Clinic in Borumeda General Hospital, Northeast Ethiopia

“…Various studies indicate that the prevalence of HBV and HCV among pregnant women becomes serious public health importance [ 7 – 9 ]. Mother-to-child transmission of HBV, which might be via intrauterine transmission, is a common phenomenon and causes chronic infection of the virus [ 10 ]. The seroprevalence of HBV among pregnant women in Ethiopia ranges from 4.5% to 7.9%, that is in line with intermediate level of endemicity of the virus [ 11 – 15 ].…”

Maternal infection with hepatitis B virus before pregnancy and risk of congenital malformations in offspring: a record-linkage study of a large national sample from China

“…Such malformations may be direct effect of infection on the embryo or fetus, or they may be indirect effects on the embryo or fetus resulting from an increase in risk of another factor contributing to fetal malformations. Direct effects may arise through germline infection, in which HBV DNA can enter oocytes, integrate into their chromosomes, and be transmitted to embryos during fertilization 21 , 50 ; paracellular infection arising through transplacental leakage early in pregnancy due to placental immaturity, or during invasive procedures such as chorionic sampling and amniocentesis 51 ; or direct infection of placental tissue. 19 , 52 Indirect effects may arise when, for example, HBV infection suppresses maternal immune responses to teratogenic viruses such as rubella, which can then move vertically from mother to fetus 53 or when HBV infection increases the risk of gestational diabetes mellitus in the mother, 54 which has been linked to greater risk of congenital malformations affecting certain systems, such as malformations affecting the cardiac system.…”

The Role of HBx Protein in Diseases Beyond the Liver

“…More than 50% of chronic HBV infections are caused by Mother-to-child transmission (MTCT) as HBV vaccines become widespread in the population. 30 However, the mechanism underlying intrauterine HBV infection remains unclear. Existing studies have shown that HBxAg can be detected in placental trophoblast cells of HBV-infected patients.…”