Association between genomic heterogeneity of hepatitis B virus and intrauterine infection

Abstract

Hepatitis B virus (HBV) intrauterine infection remains to be an important cause for a large number of persistent hepatitis B surface antigen (HBsAg) positive carriers in areas with a high HBV prevalence, particularly in China and Southeast Asia. In this study, the possible association between the HBV genomic heterogeneity and intrauterine infection was investigated by comparing the quasi species isolated from eight pairs of HBsAg-positive mothers and their neonates, who were infected intrauterinely with HBV, with clones from eight HBsAg-positive mothers whose neonates were not infected with HBV. The proportion of clones with specific mutations was compared among different subject groups, and phylogenetic analysis was performed to evaluate the significance of specific mutations. It was observed that the core promoter with conserved major functional regions and conserved hepatitis B e antigen (HBeAg) might be beneficial to HBV maternal-fetal transmission. Particularly, A1762T/G1764A mutations seemed to be disadvantageous for fetal infection. It was also shown that amino acid substitutions located in the immune epitopes of HBsAg were strongly associated with intrauterine HBV transmission. The clones with mutations such as amino acid P110S in preS1 region, P36L in preS2 region and C107R in S region might infect fetuses more readily. In addition, positively selected site analysis confirmed the above results.

Tackling the Hepatitis B Disease Burden in India

“…60,61 HBV genomic heterogeneity may also play an important role in HBV intrauterine infection and certain mutations in preS1 region, preS2 region and S region might infect fetuses more readily. 62 In south Asia, the horizontal transmission is likely occurring at a younger age group. The exact mode of horizontal transmission is not defined but it may be due to contact of non-intact skin or mucous membranes with tears, saliva or blood containing secretions or through sharing of toothbrushes.…”

High Conservation of Hepatitis B Virus Surface Genes during Maternal Vertical Transmission despite Active and Passive Vaccination

“…The characteristics of the viral genome from all pregnant women were not fully consistent, which may be related to the outcome of vertical transmission. We analyzed the relationship between HBV gene heterogeneity and intrauterine infection in previous studies, and we found that the fetuses from mothers in whose sera HBV strains had certain mutations were not easily infected [14,15] . However, there was possible confounding bias from the maternal serum HBeAg status because it was an important risk factor.…”

A novel B/C inter-genotype recombinant of hepatitis B virus identified in north-west China

“…DNA pellets were dissolved in 20 ml distilled water and 5 ml of the DNA sample was used as a template for HBV DNA amplification by PCR. Two pairs of PCR primers were used to amplify the surface and core genes, respectively, with experimental conditions described previously (Cheng et al, 2009).…”

“…The correct insert size was confirmed using PCR and the restriction enzyme SalI (Promega). Two clones were selected randomly for sequencing of the complete genome with an ABI 3730 automated DNA sequencer (Applied Biosystems) (Cheng et al, 2009;Wang et al, 2005). The two acquired HBV genomic DNAs were both 3215 bp with a high similarity of 99.9 % and thus only one of them was submitted to GenBank (accession number KC774178).…”