Overexpression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication

OBJECTIVES: 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.

CONCLUSION: 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.

Medienart:

Artikel

Erscheinungsjahr:

2006

Erschienen:

2006

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

European journal of gastroenterology & hepatology - 18(2006), 2 vom: 21. Feb., Seite 167-74

Sprache:

Englisch

Beteiligte Personen:

Siebler, Jürgen [VerfasserIn]
Protzer, Ulrike [VerfasserIn]
Wirtz, Stefan [VerfasserIn]
Schuchmann, Marcus [VerfasserIn]
Höhler, Thomas [VerfasserIn]
Galle, Peter R [VerfasserIn]
Neurath, Markus F [VerfasserIn]

Themen:

DNA, Viral
Journal Article
STAT1 Transcription Factor

Anmerkungen:

Date Completed 31.07.2006

Date Revised 07.09.2019

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM15993883X