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

Los interferones son antivirales naturales que suprimen la replicación viral bloqueando la síntesis de proteínas virales.Los interferones pegilados son un tipo de interferón recombinante creado al unir polietileno glicol a interferones.Estos interferones se unen a los receptores de las células huésped sanas y desencadenan la expresión de genes estimulados por interferón.Estos genes inducen la síntesis de varias proteínas antivirales, que inicialmente existen en estado inactivo.Tres de ellas, la proteína quinasa R, la oligoadenalato sintetasa y la RNasa L, juegan un papel clave en la interrupción de la traducción viral de ARNm.Tras la infección viral, la presencia de ARN de doble cadena viral activa estas proteínas.La proteína quinasa activa R fosforila el factor de iniciación de traducción eucariota 2⍺, impidiendo la traducción tanto del ARNm viral como del huésped.Además, la oligoadenilato sintesasa sintetiza cadenas cortas de moléculas de adenilato que activan la RNasa L.La RNasa L activa degrada entonces el ARNm viral y del huésped, deteniendo la síntesis de proteínas en las células infectadas. Esto favorece la muerte celular y limita la replicación viral.

inhibidores de la síntesis de proteínas virales

Inhibitors of Viral Protein Synthesis

La síntesis de proteínas es indispensable para la replicación viral, ya que los virus carecen de la maquinaria celular necesaria para este proceso y deben secuestrar el aparato traslacional del huésped. En respuesta, las células huésped despliegan una defensa inmunitaria innata crítica que involucra interferones, citocinas especializadas que desempeñan un papel central en la inhibición de la propagación viral.Tras la detección viral, las células infectadas liberan interferones que se unen a los receptores de células no infectadas adyacentes, activando la vía de señalización JAK-STAT y desencadenando la expresión de genes estimulados por interferón (ISG). Estos ISGs inducen la expresión de tres proteínas antivirales clave: la proteína quinasa R (PKR), la 2',5'-oligoadenilato sintetasa (OAS) y la RNasa L. El ARN bicatenario viral (dsRNA), un patrón molecular asociado a la infección, activa directamente la PKR y la OAS.El PKR activado fosforila la subunidad alfa del factor de iniciación de traducción eucariota 2 (eIF2α), deteniendo el inicio de la traducción de ARNm y suprimiendo tanto la síntesis de proteínas virales como del huésped. Simultáneamente, la EAO cataliza la producción de oligoadenilatos ligados a 2',5', que activan la RNasa L. La RNasa L activa divide el ARN viral y celular, incluido el ARN ribosómico, agravando así el apagón de la síntesis de proteínas y amplificando el estado antiviral dentro de la célula.Aplicaciones clínicas de los interferones recombinantesDadas sus potentes propiedades antivirales, los interferones recombinantes se han utilizado en el manejo clínico de varias enfermedades virales:<ul><li>Terapia antiviral: El interferón-alfa (IFN-α) ha sido una piedra angular histórica en el tratamiento de infecciones crónicas por hepatitis B y C, reduciendo la carga viral y retrasando la progresión de la enfermedad. En la hepatitis C, el interferón pegilado combinado con ribavirina era la terapia estándar antes de la aparición de los antivirales de acción directa (AAA), que ahora ofrecen una eficacia y tolerabilidad superiores. El IFN-α también se utiliza para tratar lesiones asociadas al virus del papiloma humano (VPH) y el sarcoma de Kaposi vinculado al VIH.</li><li>Oncología: IFN-α actúa como agente inmunomodulador en ciertas malignidades hematológicas, como la leucemia de células pilosas y la leucemia mieloide crónica, melanoma maligno y carcinoma de células renales.</li><li>Inmunología: El interferón-beta (IFN-β) se utiliza ampliamente para tratar la esclerosis múltiple, reduciendo la frecuencia de recaídas y retrasando la progresión de la discapacidad.</li></ul>A pesar de sus beneficios clínicos, las terapias con interferón están asociadas a efectos secundarios, incluyendo síntomas similares a los gripales, fatiga, depresión y anomalías hematológicas, que pueden limitar su uso en algunos pacientes. No obstante, estas diversas aplicaciones subrayan la versatilidad y la importancia clínica de los interferones en los ámbitos antiviral, oncológico e inmunológico.

Inhibidores de la síntesis de proteínas 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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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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