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

干扰素是一种天然抗病毒物质，通过阻断病毒蛋白质合成来抑制病毒复制。聚乙二醇化干扰素是一类通过将聚乙二醇连接到干扰素上而制成的重组干扰素。这些干扰素与健康宿主细胞上的受体结合，并触发干扰素刺激基因的表达。这些基因可诱导合成多种抗病毒蛋白，这些蛋白最初以非活性状态存在。其中三种——蛋白激酶R、寡腺苷酸合成酶和RNase L——在阻断病毒mRNA翻译过程中发挥关键作用。病毒感染后，病毒双链RNA的存在会激活这些蛋白质。活化的蛋白激酶R可磷酸化真核翻译起始因子2⍺，从而抑制病毒和宿主mRNA的翻译。此外，寡聚腺苷酸合成酶可合成寡聚腺苷酸分子短链，从而激活核糖核酸酶L。活化的RNase L随后降解病毒和宿主的mRNA，从而阻断感染细胞中的蛋白质合成。这会促进细胞死亡并限制病毒复制。

病毒蛋白合成抑制剂

Inhibitors of Viral Protein Synthesis

蛋白质合成对病毒复制至关重要，因为病毒缺乏执行该过程所需的细胞机制，必须劫持宿主的翻译装置。作为应对，宿主细胞会启动一种关键的先天免疫防御机制，涉及干扰素——一类在抑制病毒传播中发挥核心作用的特殊细胞因子。病毒被检测到后，感染细胞会释放干扰素，干扰素与邻近未感染细胞上的受体结合，激活JAK-STAT信号通路，进而触发干扰素刺激基因（ISGs）的表达。这些ISGs诱导三种关键抗病毒蛋白的表达：蛋白激酶R（PKR）、2',5'-寡腺苷酸合成酶（OAS）和RNase L。病毒双链RNA（dsRNA）是一种与感染相关的分子模式，可直接激活PKR和OAS。活化的PKR磷酸化真核翻译起始因子2的α亚基（eIF2α），从而阻断mRNA翻译的起始，抑制病毒和宿主蛋白的合成。与此同时，OAS催化生成2',5'-连接的寡聚腺苷酸，进而激活RNase L。活化的RNase L可切割病毒和细胞RNA，包括核糖体RNA，进一步加剧蛋白质合成的关闭，并增强细胞内的抗病毒状态。重组干扰素的临床应用鉴于重组干扰素具有强大的抗病毒特性，其已被用于多种病毒性疾病的临床治疗：<ul><li>抗病毒治疗：干扰素-α（IFN-α）在慢性乙型和丙型肝炎感染的治疗中曾是历史性的核心手段，可降低病毒载量并延缓疾病进展。在丙型肝炎中，聚乙二醇化干扰素联合利巴韦林曾是直接抗病毒药物（DAAs）问世前的标准疗法，而目前DAAs具有更优的疗效和耐受性。IFN-α还用于治疗人乳头瘤病毒（HPV）相关病变以及与HIV相关的卡波西肉瘤。</li><li>肿瘤学：IFN-α在某些血液系统恶性肿瘤中作为免疫调节剂使用，例如毛细胞白血病和慢性髓性白血病、恶性黑色素瘤以及肾细胞癌。</li><li>免疫学：干扰素-β（IFN-β）被广泛用于多发性硬化的管理，可减少复发频率并延缓残疾进展。</li></ul>尽管干扰素治疗具有临床益处，但也伴随一些副作用，包括流感样症状、疲劳、抑郁以及血液学异常，这些可能限制其在部分患者中的应用。然而，这些多样的应用凸显了干扰素在抗病毒、肿瘤学和免疫学领域中的多功能性及其重要的临床意义。

蛋白质合成对病毒复制至关重要，因为病毒缺乏进行该过程所需的细胞机制，必须劫持宿主的……

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Education

教育

JoVE Core

Microbiology

微生物学

Unit

单元

Antimicrobial Agents

抗微生物药物

KEY TERMS AND CONCEPTS

关键术语与概念

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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inhibitors of viral protein synthesis

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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antifungal agents

Amphotericin B and Fungal Membranes

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How Bacteria Outsmart Antibiotics

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HIV Protease Inhibitors and Maturation

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antiprotozoal agents

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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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