Overexpression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication.
OBJECTIVE
Interferons are known to inhibit the replication of hepatitis B viruses (HBV) in several animal models in vitro and in vivo as well in humans. The STAT-1 protein plays a central role in the biological activity of both type I and type II interferons. The lack of functional STAT-1 renders cells and organisms susceptible to bacterial and viral infectious agents. We analysed whether the overexpression of STAT-1 protein enhances the biological interferon response and whether it elicits antiviral activity against HBV in vitro.


METHODS
To achieve an efficient STAT-1 overexpression in primary liver cells and hepatoma cells, we generated a recombinant, replication-deficient adenovirus expressing human STAT-1 (Adv-STAT-1). We analysed whether the overexpression of STAT-1 inhibits the replication of duck HBV and human HBV in vitro using Western blot analysis, the immunofluorescence of viral proteins and quantification of HBV-DNA copies, respectively.


RESULTS
In the duck model of HBV infection the overexpression of STAT-1 neither inhibited an established infection nor prevented the establishment of duck HBV replication when administered simultaneously with Adv-STAT-1. These observations were confirmed in an in-vitro model of human HBV infection using the human hepatoma cell line HepG2.2.15, which continuously replicates HBV.


CONCLUSIONS
These data demonstrate that the over-expression of STAT-1 alone is not sufficient to strengthen the biological response of interferon as an antiviral agent.
Siebler
Jürgen
J
Labor für Klinische Immunologie I, I. Medizinische Klinik, University of Mainz, Mainz, Germany. siebler@uni-mainz.de
Protzer
Ulrike
U
Wirtz
Stefan
S
Schuchmann
Marcus
M
Höhler
Thomas
T
Galle
Peter R
PR
Neurath
Markus F
MF
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D004372:Ducks; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D004279:DNA, Viral; D050794:STAT1 Transcription Factor