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

Interferons are natural antivirals that suppress viral replication by blocking viral protein synthesis.Pegylated interferons are a type of recombinant interferon created by attaching polyethylene glycol to interferons.These interferons bind to receptors on healthy host cells and trigger the expression of interferon-stimulated genes.These genes induce the synthesis of several antiviral proteins, which initially exist in an inactive state.Three of these, protein kinase R, oligoadenylate synthetase, and RNase L, play a key role in interrupting viral mRNA translation.Upon viral infection, the presence of viral double-stranded RNA activates these proteins.Active protein kinase R phosphorylates the eukaryotic translation initiation factor 2&#9082;, preventing the translation of both viral and host mRNA.Additionally, oligoadenylate synthetase synthesizes short chains of adenylate molecules that activate RNase L.Active RNase L then degrades viral and host mRNA, halting protein synthesis in infected cells. This promotes cell death and limits viral replication.

inhibitors of viral protein synthesis

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and triggering the expression of interferon-stimulated genes (ISGs). These ISGs induce the expression of three key antiviral proteins: protein kinase R (PKR), 2',5'-oligoadenylate synthetase (OAS), and RNase L. Viral double-stranded RNA (dsRNA), a molecular pattern associated with infection, directly activates PKR and OAS.Activated PKR phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2&#945;), halting the initiation of mRNA translation and suppressing both viral and host protein synthesis. Concurrently, OAS catalyzes the production of 2',5'-linked oligoadenylates, which activate RNase L. Active RNase L cleaves viral and cellular RNA, including ribosomal RNA, thereby exacerbating the shutdown of protein synthesis and amplifying the antiviral state within the cell.Clinical Applications of Recombinant InterferonsGiven their potent antiviral properties, recombinant interferons have been utilized in the clinical management of several viral diseases:<ul><li>Antiviral therapy: Interferon-alpha (IFN-&#945;) has been a historical cornerstone in treating chronic hepatitis B and C infections, reducing viral load and delaying disease progression. In hepatitis C, pegylated interferon combined with ribavirin was standard therapy before the advent of direct-acting antivirals (DAAs), which now offer superior efficacy and tolerability. IFN-&#945; is also used to treat human papillomavirus (HPV)-associated lesions and Kaposi's sarcoma linked to HIV.</li><li>Oncology: IFN-&#945; acts as an immunomodulatory agent in certain hematologic malignancies, such as hairy cell leukemia and chronic myeloid leukemia, malignant melanoma, and renal cell carcinoma.</li><li>Immunology: Interferon-beta (IFN-&#946;) is widely used to manage multiple sclerosis, reducing relapse frequency and delaying the progression of disability.</li></ul>Despite their clinical benefits, interferon therapies are associated with side effects, including flu-like symptoms, fatigue, depression, and hematologic abnormalities, which may limit their use in some patients. Nonetheless, these diverse applications underscore the versatility and clinical significance of interferons across antiviral, oncologic, and immunologic domains.

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.

microbiology

Interferons Block Viral Replication

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