Abstract
Mutations in the hepatitis B virus (HBV) genome can potentially lead to vaccination failure, diagnostic escape, and disease progression. However, there are no reports on viral gene expression and large hepatitis B surface antigen (HBsAg) antigenicity alterations due to mutations in HBV isolated from a Bangladeshi population. Here, we sequenced the full genome of the HBV isolated from a clinically infected patient in Bangladesh. The open reading frames (ORFs) (P, S, C, and X) of the isolated HBV strain were successfully amplified and cloned into a mammalian expression vector. The HBV isolate was identified as genotype C (sub-genotype C2), serotype adr, and evolutionarily related to strains isolated in Indonesia, Malaysia, and China. Clinically significant mutations, such as preS1 C2964A, reverse transcriptase domain I91L, and small HBsAg N3S, were identified. The viral P, S, C, and X genes were expressed in HEK-293T and HepG2 cells by transient transfection with a native subcellular distribution pattern analyzed by immunofluorescence assay. Western blotting of large HBsAg using preS1 antibody showed no staining, and preS1 ELISA showed a significant reduction in reactivity due to amino acid mutations. This mutated preS1 sequence has been identified in several Asian countries. To our knowledge, this is the first report investigating changes in large HBsAg antigenicity due to preS1 mutations.
Highlights
Hepatitis B virus (HBV) is one of the smallest known animal viruses; it is known to cause acute and chronic hepatitis in humans, followed by liver cirrhosis and hepatocellular carcinoma (HCC)
These data showed that active viral replication occurred in the liver of the infected patient; this verified that the patient had no history of treatment with anti-hepatitis B virus (HBV) drugs
Silent Large hepatitis B surface antigen (HBsAg) Containing Mutated HBV Is Circulating in Asiatic Countries We found several mutations in the preS1 region that may be responsible for antigenic alterations in large HBsAg
Summary
Hepatitis B virus (HBV) is one of the smallest known animal viruses; it is known to cause acute and chronic hepatitis in humans, followed by liver cirrhosis and hepatocellular carcinoma (HCC). HBV is distributed globally with abundant mutations in its genome due to the lack of proofreading capacity in the viral polymerase protein; this genomic variability has led to what is known as quasispecies. These genomic variations show a strong association with the clinical characteristics of HBV-infected patients and geographical distribution [2]. The partially double-stranded 3.2 kb viral genome encodes four overlapping open reading frames (ORFs): P, S, C, and X. Three kinds of envelope/surface proteins are encoded by a single ORF, S, because it contains three in-frame start codons in the preS1, preS2, and S regions. The large (preS1+preS2+S), medium (preS2+S), and small (S only) surface proteins share a common C terminus region [4]
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