Inhibition of the expression of hepatitis A and B viruses (HAV and HBV) proteins by interferon in a human hepatocarcinoma cell line (PLC/PRF/5).
OBJECTIVE
PLC/PRF/5 is a continuous human hepatocarcinoma cell line whose genome contains integrated HBV DNA and which secretes two of the hepatitis B virus envelope proteins (HBs and PreS2). This line is also susceptible to infection by hepatitis A virus and was therefore used to compare the effects of interferon on protein synthesis of these two viruses and to assess the interactions which occur between them during infection.


RESULTS
Results showed that recombinant interferon alpha 2-a inhibited the expression of the two hepatitis B virus envelope antigens (HBs and PreS2) and of the only hepatitis A virus antigen in a dose-dependent fashion. Comparison of the effect of interferon on antigenic protein production of these two viruses, showed stronger inhibition of hepatitis A virus capsid antigen than of hepatitis B virus envelope antigens. Infection with hepatitis A virus also downregulates the expression of the two hepatitis B virus proteins.


CONCLUSIONS
Considering the absence of cytotoxic effects from the doses used, this study confirms the relevance of this cellular model for the study of antiviral cytokines in vitro. It also provides a further rationale for the clinical evaluation of the therapeutic potential of interferons in severe hepatitis cases due either to hepatitis A virus alone or to superinfection of hepatitis B virus carriers by hepatitis A virus.
Berthillon
P
P
INSERM U 271, Lyon, France.
Crance
J M
JM
Leveque
F
F
Jouan
A
A
Petit
M A
MA
Deloince
R
R
Trepo
C
C
D000956:Antigens, Viral / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D035921:Hepatitis A Antigens; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis*; D006515:Hepatitis B virus / Q000187:drug effects*; D006507:Hepatovirus / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000821:virology*; D011498:Protein Precursors / Q000096:biosynthesis*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D035921:Hepatitis A Antigens; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011498:Protein Precursors; D011994:Recombinant Proteins; C050807:presurface protein 2, hepatitis B surface antigen