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Struktur und Wirkung von Interferonen

  • H. Jacobsen
Chapter

Zusammenfassung

Die Interferone lassen sich begrifflich und geschichtlich auf Untersuchungen zur „viralen Interferenz“ zurückführen, die ca. 1955 von A. Isaacs und J. Lindenmann durchgeführt wurden. Virale Interferenz ist eine frühe Beobachtung in der virologischen Forschung; sie besagt, daß in vielen Virus-Wirtssystemen, Zellkultur oder Organismen, eine primäre Infektion mit Virus A eine nachfolgende Infektion mit Virus A oder nicht verwandtem Virus B, C, D hemmt. Dieser Hemmung können verschiedene Ursachen zugrunde liegen; Virus A kann z. B. den Oberflächenrezeptor für homologes oder heterologes Virus inaktivieren und somit den ersten Schritt der Virus-Zellbeziehung, die Adsorption des Virus an die Zellmembran, blockieren oder Virus A kann defekte interferierende Partikel bilden, welche selbst nicht mehr zur Replikation befähigt sind, aber die Replikation des homologen Wildtypvirus hemmen. In ihrem klassischen Experiment demonstrierten Isaac und Lindenmann eine weitere Form der Interferenz, die sich auf einen löslichen Faktor im Kultur-überstand virus-infizierter Zellen zurückführen ließ [45]. Sie infizierten Hühnereimembranen mit inaktiviertem Influenzavirus und inkubierten diese für wenige Stunden bei 37 °C. Danach übertrugen sie den Kulturüberstand auf frische Hühnereimembranen, inkubierten diese für mehrere Stunden in dem Überstand und infizierten sie anschließend mit aktivem Influenzavirus. Sie beobachteten, daß in so vorbehandelten Membranen die Virusvermehrung erheblich vermindert war. Eine solche Hemmung wurde nicht gefunden, wenn die Inkubation in Überständen von Membranen erfolgte, die nicht mit Virus behandelt waren. Isaac und Lindenmann schlössen aus diesen Befunden, daß Virus, in diesem Fall auch inaktives Virus, in infizierten Zellen die Bildung eines Faktors induziert, der sezerniert wird und in uninfizierten Zellen eine Resistenz gegen eine nachfolgende Virusinfektion bewirkt, d. h., mit Virusvermehrung interferiert. Folgerichtig wurde dieser Faktor Interferon benannt. Nachfolgende Untersuchungen etablierten schnell einige grundlegende Eigenschaften des Interferons
  1. a)

    Interferon ist ein Protein,

     
  2. b)

    Interferon hat keine Virusspezifität, d. h., durch Virus A induziertes Inter-feron hemmte Virus B, C, D und umgekehrt,

     
  3. c)

    Interferon ist artspezifisch, z. B., von Hühnerzellen produziertes Interferon hat keine Schutzwirkung auf menschliche Zellen.

     
Hieraus folgte, daß das eigentliche Ziel des Interferons nicht das Virus selbst ist, sondern die Zelle, die durch Interferon in eine Abwehrbereitschaft gegen Virusinfektion versetzt wird.

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  • H. Jacobsen

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