Evolution of Hepatitis B Virus in a Chronic HBV-Infected Patient over 2 Years

Abstract

Mutations in full-length HBV isolates obtained from a chronic HBV-infected patient were evaluated at three time points: 1 day, 6 months, and 31 months. While 5 nucleotides variation, and an 18 bp deletion of preS1 have been kept in during at least the first two years, C339T mutation occurring in the hydrophilic region of HBsAg and T770C that caused polymerase V560A substitution were the new point mutations found existing in sequenced clones of the 3rd time point. Internal deletion of coding region obviously appeared in the 3rd time point. The splicers included two new 5′-splice donors and three new 3′-splice acceptors besides the reported donors and acceptors and may have produced presumptive HBV-spliced proteins or truncated preS proteins. ALT, HBeAg and viral DNA load varied during the follow-up years. These data demonstrated the diversity of genomes in HBV-infected patient during evolution. Combined with clinical data, the HBV variants discovered in this patient may contribute to viral persistence of infection or liver pathogenesis.

BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads

“…Of the 68 SNVs identified by BAsE-Seq in S7.1, 56 confer changes in amino acid sequence, while the other 12 are silent substitutions (Table S4 in Additional file 1 ). Among the non-synonymous variants, seven are nonsense mutations (one in the open reading frame (ORF) for the HBV C protein, one in the ORF for X protein, and five in the ORF for S protein) and one is a mutation in the stop-codon of the C gene that extends the ORF by six amino acids (Table S4 in Additional file 1 ); most of these mutations have been previously described [ 42 - 44 ] or exist in sequences from GenBank. Five of the nonsense mutations are located near the end of their ORFs and consequently may reduce or alter the expression or activity of the expressed proteins rather than abolishing expression altogether.…”

Hepatitis B virus genetic mutations and evolution in liver diseases

“…Mutations at this region may directly influence HBV infection and liver disease progression. Pre-S deletion was observed in chronic hepatitis B infection, fulminant hepatitis B, acute hepatitis B and HCC [49][50][51][52][53][54][55][56][57][58] . Several crosssectional studies have shown an association between pre-S mutation and HCC [59][60][61] .…”