Virale Infektion von Hepatozyten

Zusammenfassung

Zahlreiche Viren infizieren Hepatozyten. Einerseits kann ein Verständnis der zugrunde liegenden molekularen Mechanismen genutzt werden, um eine Infektion durch pathogene Viren zu blockieren, andererseits können im Rahmen gentherapeutischer Ansätze hepatotrope Viren nutzbar gemacht werden um gezielt genetisches Material in Hepatozyten einzubringen. Das Hepatitis C Virus (HCV) folgt einem komplexen Zelleintrittsweg, der mindestens vier essenzielle Rezeptoren auf der Oberfläche der Hepatozyten nutzt. Inhibitoren des HCV Zelleintritts sind in früher klinischer Entwicklung und könnten insbesondere zur Verhinderung der HCV-Reinfektion bei Lebertransplantation nützlich sein. Über den Zelleintritt des Hepatitis B Virus und Hepatitis D Virus (HBV; HDV) ist deutlich weniger bekannt, dennoch lässt dieser sich durch aktive oder passive Immunisierung effektiv inhibieren und ein spezifischer Lipopeptid Inhibitor der auf einem Fragment der Virushülle basiert ist in klinischer Entwicklung. Weiter wird versucht hepatotrope Viren zu nutzen um genetische Defekte in Hepatozyten zu korrigieren. Insbesondere auf Adeno-assoziiertem Virus basierende Vektorsysteme zeigen hier erste ermutigende Ergebnisse.

Abstract

Many viruses infect hepatocytes. On the one hand an understanding of the underlying molecular mechanisms can be used to block infection by pathogenic viruses, on the other hand hepatotropic viruses can be utilized in gene therapy approaches for the directed delivery of genetic material into hepatocytes. The hepatitis C virus (HCV) follows a complex cell entry route utilizing at least four essential cell surface receptors on hepatocytes. Inhibitors of HCV cell entry are in early clinical development and could useful for the prevention of HCV reinfection of the graft after liver transplantation. Although much less is known about the cell entry of hepatitis B virus and hepatitis D virus (HBV; HDV) it can be blocked efficiently by active or passive immunization. Moreover, a highly specific lipopeptide entry inhibitor based on a fragment of the HBV envelope is in clinical development. Finally, approaches are being developed to use hepatotropic viruses to correct genetic defects in hepatocytes. Especially adeno-associated virus based vector systems have recently shown promising results in proof-of-concept studies.

Schlüsselwörter

Virus - Rezeptor - Hepatitis - Gentherapie

Keywords

Virus - Receptor - Hepatitis - gene therapy

• Literatur

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