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

Interferons são antivirais naturais que suprimem a replicação viral bloqueando a síntese de proteínas virais.Interferons pegilados são um tipo de interferon recombinante criado pela ligação de polietilenoglicol a interferons.Esses interferons se ligam aos receptores das células hospedeiras saudáveis e desencadeiam a expressão de genes estimulados por interferon.Esses genes induzem a síntese de várias proteínas antivirais, que inicialmente existem em estado inativo.Três delas, proteína quinase R, oligoadenilato sintetase e RNase L, desempenham um papel fundamental na interrupção da tradução viral de mRNA.Após a infecção viral, a presença de RNA de fita dupla ativa essas proteínas.A proteína cinese ativa R fosforila o fator de iniciação de tradução eucariótica 2⍺, impedindo a tradução tanto do mRNA viral quanto do hospedeiro.Além disso, a oligoadenilato sintetase sintetiza cadeias curtas de moléculas de adenilato que ativam a RNase L.A RNase L ativa então degrada o mRNA viral e do hospedeiro, interrompendo a síntese proteica nas células infectadas. Isso promove a morte celular e limita a replicação viral.

inibidores da síntese de proteínas virais

Inhibitors of Viral Protein Synthesis

A síntese proteica é indispensável para a replicação viral, pois os vírus não possuem a maquinaria celular necessária para esse processo e precisam sequestrar o aparato translacional do hospedeiro. Em resposta, as células hospedeiras utilizam uma defesa imune inata crítica envolvendo interferons, citocinas especializadas que desempenham um papel central na inibição da propagação viral.Após a detecção viral, as células infectadas liberam interferons que se ligam a receptores em células adjacentes não infectadas, ativando a via de sinalização JAK-STAT e desencadeando a expressão de genes estimulados por interferon (ISGs). Esses ISGs induzem a expressão de três proteínas antivirais principais: proteína quinase R (PKR), 2',5'-oligoadenilato sintetase (OAS) e RNase L. O RNA viral de fita dupla (dsRNA), um padrão molecular associado à infecção, ativa diretamente a PKR e a OAS.O PKR ativado fosforila a subunidade alfa do fator de iniciação de tradução eucariótica 2 (eIF2α), interrompendo o início da tradução de mRNA e suprimindo tanto a síntese viral quanto a de proteínas do hospedeiro. Simultaneamente, a OAS catalisa a produção de oligoadenilatos ligados a 2',5', que ativam a RNase L. A RNase L ativa cliva RNas virais e celulares, incluindo RNA ribossomal, agravando assim o desligamento da síntese proteica e amplificando o estado antiviral dentro da célula.Aplicações clínicas dos interferons recombinantesDadas suas potentes propriedades antivirais, os interferons recombinantes têm sido utilizados no manejo clínico de várias doenças virais:<ul><li>Terapia antiviral: O interferon-alfa (IFN-α) tem sido uma pedra angular histórica no tratamento de infecções crônicas por hepatite B e C, reduzindo a carga viral e retardando a progressão da doença. Na hepatite C, o interferon pegilado combinado com ribavirina era a terapia padrão antes do advento dos antivirais de ação direta (AAD), que agora oferecem eficácia e tolerabilidade superiores. O IFN-α também é usado para tratar lesões associadas ao papilomavírus humano (HPV) e o sarcoma de Kaposi ligados ao HIV.</li><li>Oncologia: O IFN-α atua como agente imunomodulador em certas malignidades hematológicas, como leucemia de células pilosas, leucemia mieloide crônica, melanoma maligno e carcinoma de células renais.</li><li>Imunologia: O interferon-beta (IFN-β) é amplamente utilizado para tratar a esclerose múltipla, reduzindo a frequência de recaídas e atrasando a progressão da incapacidade.</li></ul>Apesar de seus benefícios clínicos, as terapias com interferon estão associadas a efeitos colaterais, incluindo sintomas semelhantes aos da gripe, fadiga, depressão e anormalidades hematológicas, que podem limitar seu uso em alguns pacientes. No entanto, essas diversas aplicações ressaltam a versatilidade e a importância clínica dos interferons nos domínios antiviral, oncológico e imunológico.

Inibidores da Síntese de Proteínas Virais

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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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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