Effect of interferon-γ on hepatitis B viral antigen expression in primary hepatocyte culture

Abstract

Interferon-alpha has been shown recently to selectively enhance hepatocyte expression of HBsAg/pre-S2 in chronic hepatitis B virus infection in a way that may enhance immune recognition. To determine the effect of interferon-gamma on hepatitis B virus antigen expression, hepatocytes isolated from patients with chronic hepatitis B virus infection were incubated in the absence or presence of interferon-gamma and viral antigen expression was assessed by both radioimmunoassay and immunocytochemistry using appropriate monoclonal antibodies. Interferon-gamma inhibited the expression of all hepatitis B virus antigens tested. Intracellular HBsAg measured by radioimmunoassay of sonicated hepatocytes fell by 29% with 1 U/ml (p less than 0.01) and 36% with 10 U/ml of interferon-gamma (p less than 0.001) compared with control treatment. Secreted HBsAg was reduced by 19% with 10 U/ml of interferon-gamma (p less than 0.01). Intracellular HBeAg was also decreased by 29% with 1 U/ml (p less than 0.05) and 42% with 10 U/ml of interferon-gamma (p less than 0.05), but no significant change was found in the amount of secreted HBeAg. The proportion of hepatocytes containing various hepatitis B virus antigens and the intracellular viral antigen staining densities also fell significantly with interferon-gamma incubation. Interestingly, the addition of interferon-gamma abolished the augmenting effect of interferon-alpha on intracellular HBsAg. These data indicate that interferon-gamma, in contrast to interferon-alpha, has an inhibitory effect on hepatocyte expression of all hepatitis B virus antigens including HBsAg/pre-S2, suggesting that this may be one factor that accounts for their difference in clinical activity in patients with chronic hepatitis B virus infection.

Inhibition of duck hepatitis B virus replication by interferon‐γ

“…In accord with our findings, they also ob-ments. Although we do not fully understand the reasons for the discrepancies between these findings and those reported here and by Lau et al [1991], several factors may contribute. Among the obvious ones are different viruses (DHBV versus HBV), different host cell lines (Huh 7 versus HepGB), and different IFN preparations.…”

“…Other investigators have examined the effect of IFN-y on HBV expression in alternate systems. Lau et al [1991], using radioimmunoassay and immunocytochemistry on primary hepatocytes isolated from carriers of HBV, found that recombinant IFN-y had a significant inhibitory effect on hepatocyte expression of all intracellular hepatitis B virus antigens. These findings are consistent with our results, and indicate that our findings are likely to be relevant to human HBV infection.…”

Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B

“…The viability of the isolated hepatocytes assessed in parallel by trypan blue dye exclusion and by plastic adherence and eosin staining after 16-h culture was >75%. This result was comparable to the numbers of viable cells observed after short-term culture using similar assays in previous studies [24,25].…”

Chronic Hepatitis B: Current and Future Treatment Options

“…4,5 In hepatitis B, IFN-␣-2b works by inhibiting viral RNA pregenomic packaging into core particles and by enhancing the expression of HBsAg on hepatocytes. 6,7 Many randomized, controlled trials involving Asian, European, and North American subjects have demonstrated that IFN-␣-2b suppresses replication of HBV. [8][9][10][11][12] The efficacy of IFN-␣-2b therapy is evidenced by loss of HBeAg and HBV DNA, which occurs in up to 30-40% of patients 1 year after the start of treatment.…”