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

Les interférons sont des antiviraux naturels qui suppriment la réplication virale en bloquant la synthèse des protéines virales.Les interférons pégylés sont un type d’interféron recombinant créé par l’attachement du polyéthylène glycol aux interférons.Ces interférons se lient aux récepteurs des cellules hôtes saines et déclenchent l’expression de gènes stimulés par l’interféron.Ces gènes induisent la synthèse de plusieurs protéines antivirales, qui existent initialement à l’état inactif.Trois d’entre elles, la protéine kinase R, l’oligoadénylate synthétase et la RNase L, jouent un rôle clé dans l’interruption de la traduction virale de l’ARNm.En cas d’infection virale, la présence d’ARN bibrin viral active ces protéines.La kinase protéique active R phosphoryle le facteur d’initiation de la traduction eucaryote 2⍺, empêchant la traduction à la fois de l’ARNm viral et de l’ARNm de l’hôte.De plus, l’oligoadénylate synthétase synthétise de courtes chaînes de molécules d’adénylate qui activent la RNase L.La RNase L active dégrade alors l’ARNm viral et l’hôte, stoppant la synthèse des protéines dans les cellules infectées. Cela favorise la mort cellulaire et limite la réplication virale.

inhibiteurs de la synthèse des protéines virales

Inhibitors of Viral Protein Synthesis

La synthèse des protéines est indispensable à la réplication virale, car les virus ne disposent pas de la machinerie cellulaire nécessaire à ce processus et doivent détourner l’appareil translationnel de l’hôte. En réponse, les cellules hôtes déploient une défense immunitaire innée critique impliquant des interférons, des cytokines spécialisées qui jouent un rôle central dans l’inhibition de la propagation virale.Lors de la détection virale, les cellules infectées libèrent des interférons qui se lient aux récepteurs des cellules adjacentes non infectées, activant la voie de signalisation JAK-STAT et déclenchant l’expression de gènes stimulés par l’interféron (ISG). Ces ISG induisent l’expression de trois protéines antivirales clés : la kinase protéique R (PKR), la 2',5'-oligoadénylate synthétase (OAS) et la RNase L. L’ARN viral double brin (dsRNA), un motif moléculaire associé à l’infection, active directement la PKR et l’OAS.Le PKR activé phosphoryle la sous-unité alpha du facteur d’initiation de traduction eucaryote 2 (eIF2α), arrêtant l’initiation de la traduction de l’ARNm et supprimant à la fois la synthèse des protéines virales et de l’hôte. Parallèlement, l’OAS catalyse la production d’oligoadénylates liés à 2',5', qui activent la RNase L. La RNase L active fende l’ARN viral et cellulaire, y compris l’ARN ribosomique, aggravant ainsi l’arrêt de la synthèse protéique et amplifiant l’état antiviral au sein de la cellule.Applications cliniques des interférons recombinantsCompte tenu de leurs puissantes propriétés antivirales, les interférons recombinants ont été utilisés dans la prise en charge clinique de plusieurs maladies virales :<ul><li>Traitement antiviral : L’interféron-alpha (IFN-α) a été une pierre angulaire historique dans le traitement des infections chroniques à l’hépatite B et C, réduisant la charge virale et retardant la progression de la maladie. Dans l’hépatite C, l’interféron pégylé combiné à la ribavirine était une thérapie standard avant l’apparition des antiviraux à action directe (AAD), qui offrent désormais une efficacité et une tolérabilité supérieures. L’IFN-α est également utilisé pour traiter les lésions associées au papillomavirus humain (HPV) et le sarcome de Kaposi lié au VIH.</li><li>Oncologie : L’IFN-α agit comme agent immunomodulateur dans certaines malignités hématologiques, telles que la leucémie à cellules pileuses, la leucémie myéloïde chronique, le mélanome malin et le carcinome à cellules rénales.</li><li>Immunologie : L’interféron-bêta (IFN-β) est largement utilisé pour gérer la sclérose en plaques, réduisant la fréquence des rechutes et retardant la progression de l’incapacité.</li></ul>Malgré leurs bénéfices cliniques, les thérapies par interféron sont associées à des effets secondaires, notamment des symptômes grippaux, de la fatigue, de la dépression et des anomalies hématologiques, ce qui peut limiter leur utilisation chez certains patients. Néanmoins, ces applications diverses soulignent la polyvalence et l’importance clinique des interférons dans les domaines antiviral, oncologique et immunologique.

Inhibiteurs de la synthèse des protéines virales

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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Antimicrobial Agents

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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.

microbiology

Interferons Block Viral Replication

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