Influence of HBV Genotypes on Disease Parameters

In patients with chronic hepatitis C virus (HCV) infection, viral genotype is an important determinant of response to therapy; however, the role of hepatitis B virus (HBV) genotype is less clear.

In a report in the October 2006 issue of Hepatology, Japanese researchers noted that various HBV genotypes induce liver disease of distinct severity, but the underlying virological differences are not well defined.

To explore this issue, Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different viral genotypes/subgenotypes (2 strains each for types Aa/A1, Ae/A2, Ba/B2 and D; 3 each for types Bj/B1 and C).

Results

HBV DNA levels in cell lysates were highest for type C, followed by Bj/Ba and D/Ae (P < 0.01).

HBV DNA levels were lowest for type Aa (P < 0.01).

In culture media, HBV DNA levels were the highest for type Bj, distantly followed by types Ba/C/D, and further by types Ae/Aa (P < 0.01).

The intracellular expression of HBV core protein was more than 3-fold lower for type Ae/Aa than the others.

Hepatitis B "e" antigen (HBeAg) was excreted in a pattern similar to that of HBV DNA, but with smaller differences.

Secretion of hepatitis B surface antigen (HBsAg) was most abundant for type Ae, followed by types Aa, Ba, Bj/C, and remotely by type D, which was consistent with mRNA levels.

Cellular stress determined by the reporter assay for Grp78 promoter was higher for types C and Ba than other genotypes/subgenotypes (P < 0.01).

Severe combined immunodeficiency mice transgenic for urokinase-type plasminogen activator (uPA/SCID) with human hepatocytes were inoculated with virions passed in mouse and recovered from culture supernatants.

HBV DNA levels in mouse sera were higher for type C than Ae by 2 logs at 4-7 weeks after inoculation.

Conclusion

In conclusion, the authors wrote, "virological differences among HBV genotypes were demonstrated both in vitro and in vivo. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings."

Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

10/10/06

Reference
M Sugiyama, Y Tanaka, T Kato, and others. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology 44(4): 915-924. October 2006.