Evolution of Hepatitis B virus in an acute hepatitis B patient co-infected with genotypes B and C

The interactions between different genotypes of Hepatitis B virus (HBV) in co-infected patients remain largely unknown, especially in acute infection. Here, the evolution of HBV strains was studied in an acute, self-limited hepatitis B patient co-infected with genotypes Ba (B2) and C. Virological analyses were performed at four time points after admission: T1 (5 days), T2 (11 days), T3 (22 days) and T4 (260 days). A dominant-genotype change from genotype C to Ba was found after anti-HBV e antigen (anti-HBe) seroconversion. Further clonal and phylogenetic analyses of the pre-S and pre-core/core regions of HBV were carried out to clarify the interactions between genotypes Ba and C. All clones propagated from T1 and T2 were of genotype C. In contrast, clones propagated from T3 (after anti-HBe seroconversion) were of genotype Ba, C and/or recombinant within the pre-S region. At T4, all clones were of genotype Ba with a 123 bp (from nt 3147 of the pre-S1 region to nt 54 of the pre-S2 region) in-frame pre-S deletion and had lost the start codon of the middle envelope protein and the nucleocapsid-binding site. Phylogenetic analysis showed that genetic distance was greater at T3 after seroconversion to anti-HBe. By using SimPlot, the breakpoint of one pre-S recombinant was located at nt 3069–3100 and the other two at nt 49–87. In conclusion, HBV genotype Ba may overtake genotype C as the predominant strain after anti-HBe seroconversion in acute hepatitis B. Recombination within the pre-S region emerged transiently and the pre-S deletion mutant was finally cleared.