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

Gli interferoni sono antivirali naturali che sopprimono la replicazione virale bloccando la sintesi delle proteine virali.Gli interferoni pegilati sono un tipo di interferone ricombinante creato collegando il poliglicole agli interferoni.Questi interferoni si legano ai recettori sulle cellule ospiti sane e stimolano l'espressione di geni stimolati dall'interferone.Questi geni inducono la sintesi di diverse proteine antivirali, che inizialmente esistono in uno stato inattivo.Tre di questi, proteina chinasi R, oligoadenilato sintetasi e RNasi L, svolgono un ruolo chiave nell'interrompere la traduzione virale dell'mRNA.In caso di infezione virale, la presenza di RNA a doppio filamento virale attiva queste proteine.La proteina chinasi attiva R fosforila il fattore di innanziamento della traduzione eucariotica 2⍺, impedendo la traduzione sia dell'mRNA virale che dell'ospite.Inoltre, l'oligoadenilato sintetasi sintetizza catene corte di molecole di adenilato che attivano RNasi L.La RNasi L attiva quindi degrada l'mRNA virale e dell'ospite, interrompendo la sintesi proteica nelle cellule infette. Questo favorisce la morte cellulare e limita la replicazione virale.

inibitori della sintesi proteica virale

Inhibitors of Viral Protein Synthesis

La sintesi proteica è indispensabile per la replicazione virale, poiché i virus non dispongono della macchina cellulare necessaria per questo processo e devono dirottare l'apparato traslazionale dell'ospite. In risposta, le cellule ospiti impiegano una difesa immunitaria innata critica che coinvolge interferoni, citochine specializzate che svolgono un ruolo centrale nell'inibizione della propagazione virale.Al momento della rilevazione virale, le cellule infette rilasciano interferoni che si legano ai recettori delle cellule non infette adiacenti, attivando la via di segnalazione JAK-STAT e innescando l'espressione di geni stimolati dall'interferone (ISG). Questi ISG inducono l'espressione di tre proteine antivirali chiave: protein chinasi R (PKR), 2',5'-oligoadenilato sintetasi (OAS) e RNasi L. L'RNA a doppio filamento virale (dsRNA), un pattern molecolare associato all'infezione, attiva direttamente PKR e OAS.Il PKR attivato fosforila la subunità alfa del fattore di iniziazione della traduzione eucariotica 2 (eIF2α), bloccando l'inizio della traduzione dell'mRNA e sopprimendo sia la sintesi virale che quella delle proteine ospiti. Contemporaneamente, l'OAS catalizza la produzione di oligoadenilati legati a 2',5', che attivano RNasi L. La RNasi L attiva divide l'RNA virale e cellulare, incluso l'RNA ribosomico, aggravando così lo spegnimento della sintesi proteica e amplificando lo stato antivirale all'interno della cellula.Applicazioni cliniche degli interferoni ricombinantiDate le loro potenti proprietà antivirali, gli interferoni ricombinanti sono stati utilizzati nella gestione clinica di diverse malattie virali:<ul><li>Terapia antivirale: l'interferone-alfa (IFN-α) è stato una pietra miliare storica nel trattamento delle infezioni croniche da epatite B e C, riducendo il carico virale e ritardando la progressione della malattia. Nell'epatite C, l'interferone pegilato combinato con ribavirina era la terapia standard prima dell'avvento degli antivirali ad azione diretta (DAA), che ora offrono efficacia e tollerabilità superiori. L'IFN-α viene anche utilizzato per trattare lesioni associate al papillomavirus umano (HPV) e il sarcoma di Kaposi legato all'HIV.</li><li>Oncologia: IFN-α agisce come agente immunomodulatore in alcune neoplasie ematologiche, come la leucemia a cellule pilose, la leucemia mieloide cronica, il melanoma maligno e il carcinoma a cellule renali.</li><li>Immunologia: l'interferone-beta (IFN-β) è ampiamente utilizzato per gestire la sclerosi multipla, riducendo la frequenza delle ricadute e ritardando la progressione della disabilità.</li></ul>Nonostante i loro benefici clinici, le terapie con interferone sono associate a effetti collaterali, tra cui sintomi influenzali, affaticamento, depressione e anomalie ematologiche, che possono limitarne l'uso in alcuni pazienti. Tuttavia, queste diverse applicazioni sottolineano la versatilità e l'importanza clinica degli interferoni nei campi antivirali, oncologici e immunologici.

Inibitori della sintesi proteica virale

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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