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The hepatitis B virus may be transmitted through the placenta from one cell to another rather than being transmitted by blood. Antibodies against the virus may carry it from one cell to another because the cells have receptors for the antibody.

There are many factors leading to intrauterine infection with hepatitis B virus (HBV). These factors include viral structure, HBV mutations, HBV DNA level, placenta barrier, immune status of the mother, and susceptibility of the fetus. The purpose of this study was to investigate the possible relationship between intrauterine infection with and HBV mutations of the genome of the virus. In this study, HBsAg‐positive mothers were divided into two groups: intrauterine infection group and non‐infection group according to whether the newborn infants were infected or not. The intrauterine infection group included four pairs of mother and their newborn infants infected in utero, and non‐infection group included five HBsAg‐positive mothers. HBV sequences from the two groups were analyzed and compared. The predominant strains in the mothers and infants from the intrauterine infection group were not completely consistent. This suggested that both HBV predominant strains and minority strains in the mothers could infect their infants through intrauterine transmission. Some HBV mutations probably related to intrauterine infection were examined and it was found that the frequencies of mutations were low in isolates of the virus of infants from the intrauterine infection group and high in the non‐infection group. These results suggest that some strains of HBV from the mother may be transmitted selectively to the fetus in utero because of viral heterogeneity. The strains without screened mutations such as P21L in the pre‐S1 region may infect the fetus more readily. J. Med. Virol. 77:180–187, 2005. © 2005 Wiley‐Liss, Inc.

Previous studies reported that the HBV DNA level in maternal serum is an important risk factor for intrauterine infection. Two antiviral drugs, lamivudine (3TC) and interferon α (IFNα), are used extensively clinically to reduce maternal HBV DNA level, However, because of a lack of evidence on the efficacy and safety of these drugs during pregnancy, they are categorized as grade C which prevents their use during pregnancy. This study provides new data on the efficacy and safety of lamivudine and IFNα in HBV positive transgenic pregnant mice. In this study, transgenic mice with high titers of hepatitis B virus (HBV) were employed to study the antiviral effects of 3TC and IFNα during different gestation periods. The study also examined changes in several serological HBV markers, the effects of perinatal exposure to antiviral drugs on the mother and offspring, drug efficacy in reducing the level of HBV DNA in maternal blood, and the safety to both the mother and offspring. The main conclusion of the study is that a significant decrease in HBV DNA level can be obtained after treatment with lamivudine but not with IFNα. No adverse effects were observed in the maternal mice and the offsprings. This finding may provide a rationale for the potential use of lamivudine for the treatment of pregnant women as a safe and effective measure to reduce the level of maternal viremia. J. Med. Virol. 76:203–207, 2005. © 2005 Wiley‐Liss, Inc.

Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case‐control study included 402 newborn infants from 402 HBsAg‐positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full‐term placentas from the HBsAg‐positive pregnant women above and 14 from HBsAg‐negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR = 17.07, 95%CI 3.39–86.01) and threatened preterm labor (OR = 5.44, 95%CI 1.15–25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P= 0.0117) and HBV DNA concentration (trend test P< 0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P= 0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR = 18.46, P= 0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a “cellular transfer” of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed. J. Med. Virol. 67:20–26, 2002. © 2002 Wiley‐Liss, Inc.

Chondrocytes have been shown to produce superoxide and hydrogen peroxide, suggesting possible formation of hydroxyl radical in these cells. In this study, we used electron spin resonance/spin trapping technique to detect hydroxyl radicals in chondrocytes. We found that hydroxyl radicals could be detected as α-hydroxyethyl spin trapped adduct of 4-pyridyl 1-oxide N-tert-butylnitrone (4-POBN) in chondrocytes stimulated with phorbol 12-myristate 13-acetate in the presence of ferrous ion. The formation of hydroxyl radical appears to be mediated by the transition metal-catalyzed Haber-Weiss reaction since no hydroxyl radical was detected in the absence of exogenous iron. The hydroxyl radical formation was inhibited by catalase but not by superoxide dismutase, suggesting that the hydrogen peroxide is the precursor. Cytokines, IL-1 and TNF enhanced the hydroxyl radical formation in phorbol 12-myristate 13-acetate treated chondrocytes. Interestingly, hydroxyl radical could be detected in unstimulated fresh human and rabbit cartilage tissue pieces in the presence of iron. These results suggest that the formation of hydroxyl radical in cartilage could play a role in cartilage matrix degradation.

Deoxyhypusine synthase is an NAD+-dependent enzyme that catalyses the formation of a deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor by transferring an aminobutyl moiety from spermidine to the ε-amino group of a unique lysine residue. We have recently cloned and characterized the Neurospora crassa deoxyhypusine synthase cDNA using a reverse genetics approach. A GenBank search showed that a stretch of the deduced amino acid sequence (96 amino acids) of Neurospora deoxyhypusine synthase matches a short human expressed sequence tag (EST), Z25337, with greater than 70% amino acid identity. Gene-specific primers based on this EST were used together with universal primers to obtain 1219 bp and 1078 bp cDNAs from a human cDNA library. The 1219 bp and 1078 bp sequences, each containing an open reading frame, encode polypeptides of respectively 368 and 321 amino acids. The short sequence is identical to the long one except that it is missing a stretch of 47 amino acids spanning residues 261–307. The 368-amino-acid sequence of human deoxyhypusine synthase shares a high degree of identity (> 50%) and similarity (> 60%) with that of the Neurospora and yeast deoxyhypusine synthases. After cloning into an expression vector, the 368-amino-acid recombinant protein exhibits high deoxyhypusine synthase activity. In contrast, the 321-amino-acid recombinant protein shows no detectable activity.