Name: interferons block viral replication
Uploaded: 2026-03-12T13:36:03.000Z
Duration: 1 min 30 s
Channel: JoVE

Interferone sind natürliche antivirale Mittel, die die virale Replikation unterdrücken, indem sie die Synthese viraler Proteine blockieren.Pegylierte Interferone sind eine Art rekombinantes Interferon, das durch Anbindung von Polyethylenglykol an Interferone entsteht.Diese Interferone binden an Rezeptoren gesunder Wirtszellen und lösen die Expression interferonstimulierter Gene aus.Diese Gene induzieren die Synthese mehrerer antiviraler Proteine, die zunächst inaktiv sind.Drei davon, Proteinkinase R, Oligoadenylatsynthetase und RNase L, spielen eine Schlüsselrolle bei der Unterbrechung der viralen mRNA-Translation.Bei einer Virusinfektion aktiviert das Vorhandensein von viraler doppelsträngiger RNA diese Proteine.Das aktive Protein-Kinase R phosphoryliert den eukaryotischen Translationsinitiationsfaktor 2⍺ und verhindert so die Translation sowohl der viralen als auch der Wirts-mRNA.Zusätzlich synthetisiert Oligoadenylatsynthetase kurze Ketten von Adenylatmolekülen, die RNase L aktivieren.Die aktive RNase L baut dann virale und wirts-mRNA ab und stoppt die Proteinsynthese in infizierten Zellen. Dies fördert den Zelltod und begrenzt die virale Replikation.

inhibitoren der viralen proteinsynthese

Inhibitors of Viral Protein Synthesis

Die Proteinsynthese ist für die virale Replikation unverzichtbar, da Viren nicht über die zelluläre Maschinerie verfügen, die für diesen Prozess erforderlich sind, und sie das translationale Apparat des Wirts kapern müssen. Als Reaktion darauf setzen Wirtszellen eine kritische angeborene Immunabwehr ein, die Interferone umfasst, spezialisierte Zytokine, die eine zentrale Rolle bei der Hemmung der viralen Verbreitung spielen.Nach viraler Entdeckung setzen infizierte Zellen Interferone frei, die an Rezeptoren auf benachbarten uninfizierten Zellen binden, wodurch der JAK-STAT-Signalweg aktiviert und die Expression interferonstimulierter Gene (ISGs) ausgelöst wird. Diese ISGs induzieren die Expression von drei zentralen antiviralen Proteinen: Proteinkinase R (PKR), 2',5'-Oligoadenylatsynthetase (OAS) und RNase L. Virale Doppelsträng-RNA (dsRNA), ein molekulares Muster, das mit einer Infektion assoziiert ist, aktiviert PKR und OAS direkt.Aktivierte PKR phosphoryliert die Alpha-Untereinheit des eukaryotischen Translationsinitiationsfaktors 2 (eIF2α), stoppt die Initiierung der mRNA-Translation und unterdrückt sowohl die Synthese des viralen als auch des Wirtsproteins. Gleichzeitig katalysiert OAS die Produktion von 2',5'-gebundenen Oligoadenylaten, die RNase L aktivieren. Die aktive RNase L spaltet virale und zelluläre RNA, einschließlich ribosomaler RNA, und verschärft so den Stillstand der Proteinsynthese und verstärkt den antiviralen Zustand innerhalb der Zelle.Klinische Anwendungen rekombinanter InterferoneAufgrund ihrer starken antiviralen Eigenschaften wurden rekombinante Interferone in der klinischen Behandlung verschiedener Viruserkrankungen eingesetzt:<ul><li>Antivirale Therapie: Interferon-alpha (IFN-α) ist ein historischer Eckpfeiler bei der Behandlung chronischer Hepatitis-B- und C-Infektionen, reduziert die Viruslast und verzögert den Krankheitsverlauf. Bei Hepatitis C war pegyliertes Interferon in Kombination mit Ribavirin die Standardtherapie, bevor es direkt wirkende antivirale Medikamente (DAAs) gab, die heute eine überlegene Wirksamkeit und Verträglichkeit bieten. IFN-α wird auch zur Behandlung von humanen Papillomavirus-(HPV)-assoziierten Läsionen und dem mit HIV verbundenen Kaposi-Sarkom eingesetzt.</li><li>Onkologie: IFN-α wirkt als immunmodulierendes Mittel bei bestimmten hämatologischen Malignitäten, wie Haarzellleukämie und chronischer myeloischer Leukämie, bösartigem Melanom und Nierenzellkarzinom.</li><li>Immunologie: Interferon-Beta (IFN-β) wird weit verbreitet zur Behandlung der Multiplen Sklerose eingesetzt, wodurch die Rückfallhäufigkeit reduziert und das Fortschreiten der Behinderung verzögert wird.</li></ul>Trotz ihrer klinischen Vorteile sind Interferontherapien mit Nebenwirkungen verbunden, darunter grippeähnliche Symptome, Müdigkeit, Depressionen und hämatologische Auffälligkeiten, die ihre Anwendung bei einigen Patienten einschränken können. Dennoch unterstreichen diese vielfältigen Anwendungen die Vielseitigkeit und klinische Bedeutung von Interferonen in antiviralen, onkologischen und immunologischen Bereichen.

Inhibitoren der viralen Proteinsynthese

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's ...

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interferons block viral replication

Interferons block viral replication by shutting down protein synthesis and activating the cell’s antiviral defenses. Viruses need the host cell’s translational machinery to make proteins, because they do not have the machinery to do this on their own. When a virus is detected, infected cells release interferons, which are cytokines, or signaling proteins, that warn nearby uninfected cells.

Interferons bind to receptors on nearby cells and activate the JAK-STAT signaling pathway. This turns on interferon-stimulated genes, or ISGs. These genes lead to the production of three key antiviral proteins: protein kinase R (PKR), 2',5'-oligoadenylate synthetase (OAS), and RNase L.

Viral double-stranded RNA, or dsRNA, helps activate PKR and OAS. PKR phosphorylates the alpha subunit of eukaryotic translation initiation factor 2, called eIF2alpha. This blocks the start of mRNA translation and slows both viral and host protein synthesis. At the same time, OAS makes 2',5'-linked oligoadenylates, which activate RNase L.

Active RNase L breaks down viral and cellular RNA, including ribosomal RNA. This deepens the shutdown of protein synthesis and strengthens the antiviral state in the cell. Recombinant interferons have also been used in medicine, especially for chronic hepatitis B and C, HPV-associated lesions, and Kaposi's sarcoma linked to HIV.

Interferon-alpha, or IFN-alpha, was a historical treatment for hepatitis C before direct-acting antivirals became available. Pegylated interferon with ribavirin was once standard therapy for hepatitis C. IFN-alpha is also used in some cancers, including hairy cell leukemia, chronic myeloid leukemia, malignant melanoma, and renal cell carcinoma.

Interferon-beta, or IFN-beta, is used to manage multiple sclerosis. It can reduce relapse frequency and slow disability progression. Interferon treatments can also cause flu-like symptoms, fatigue, depression, and blood-related abnormalities, which may limit their use.

Interferons Block Viral Replication

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Interferons block viral replication by shutting down protein synthesis and activating the cell’s antiviral defenses. Viruses need the host cell’s translational machinery to make proteins, because they do not have the machinery to do this on their own. When a virus is detected, infected cells release interferons, which are cytokines, or signaling proteins, that warn nearby uninfected cells. Interferons bind to receptors on nearby cells and activate the JAK-STAT signaling pathway. This turns on...

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key terms and concepts

Learn how interferons stop viral replication by turning on PKR, OAS, and RNase L, and see their uses in hepatitis, HPV, cancer, and multiple sclerosis.

Interferons Block Viral Replication | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

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Interferons Block Viral Replication

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