INTERFERON IN VIRAL-HEPATITIS - ROLE IN PATHOGENESIS AND TREATMENT
INTERFERON IN VIRAL-HEPATITIS - ROLE IN PATHOGENESIS AND TREATMENT
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DOI：
10.1002/hep.1840060537
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发表时间：
1986-09-01
期刊：
影响因子：
13.5
通讯作者：
HOOFNAGLE, JH
中科院分区：
文献类型：
--
作者：
DAVIS, GL;HOOFNAGLE, JH
干扰素是由有核细胞对病毒应答产生的宿主衍生蛋白质，代表对病毒感染的早期抗体前应答（1）。已经描述了由不同细胞群产生的三种一般类型的干扰素。α-干扰素由B淋巴细胞和单核细胞产生，β-干扰素由成纤维细胞产生，γ-或免疫干扰素由T淋巴细胞的辅助/诱导亚群产生（2）。干扰素在极低浓度（fmol/ml）下具有活性，并通过与特异性细胞受体结合（3）和激活细胞内酶（例如，2 '，5'-寡腺苷酸合成酶）在细胞内引发抗病毒反应，该酶导致产生短寡核苷酸，在dsRNA存在下，该短寡核苷酸激活核糖核酸酶（4）。已经表明，这些破坏感染细胞内病毒mRNA的核糖核酸酶的激活是干扰素抑制病毒复制的主要机制（4）。然而，干扰素也可以抑制病毒进入靶细胞和其他随后的复制事件（脱壳，翻译和组装）（1）。干扰素除了具有直接的抗病毒作用外，还具有其他性质，这可能使它们在通过免疫机制限制和根除急性病毒感染方面发挥重要作用。干扰素具有多种免疫调节作用。干扰素增强病毒感染细胞膜上的HLA I类抗原表达（5），激活识别细胞膜上病毒HLA抗原复合物的抗原加工细胞，并聚集特异性细胞毒性T淋巴细胞应答（6，7），它们增强自然杀伤细胞活性（8）。它们通过降低病毒感染细胞对这种攻击的抗性而增加未感染细胞的攻击阈值来进一步指导细胞毒性T淋巴细胞应答（9，10）。干扰素已被证明可以限制病毒从感染病灶部位的传播（II），缩短病毒血症期并降低急性全身感染的严重程度（12）。由于干扰素在正常人的血清中通常检测不到，因此在各种病毒感染患者的血清中发现干扰素水平高达数百单位/毫升也支持其在急性病毒感染中的作用（13）。
Interferons are host-derived proteins produced by nucleated cells in response to viruses and represent the early, preantibody, response to viral infection (1). Three general types of interferon produced by different cell populations have been described. a-Interferon is produced by B-lymphocytes and monocytes,@-interferon by fibroblasts, and y-or immune interferon by the helper/inducer subset of T-lymphocytes (2). Interferons are active at extremely low concentrations (fmoles per milliliter) and elicit an antiviral response in cells by binding to specific cell receptors (3) and activating intracellular enzymes, eg, 2’, 5’-oligoadenylate synthetase which leads to production of short oligonucleotides that, in the presence of dsRNA, activates ribonucleases (4). It has been suggested that the activation of these ribonucleases which destroy viral mRNAs within infected cells is the major mechanism by which interferons inhibit viral replication (4). However, interferons may also inhibit virus entry and other subsequent replicative events (uncoating, translation and assembly) within the target cell (1). Interferons have other properties besides their direct antiviral actions which may make them important in limiting and eradicating acute virus infection via immune mechanisms. Interferons have several immunomodulatory actions. Interferons amplify HLA Class I antigen expression on membranes of virus-infected cells (5), activate antigen-processing cells which recognize viral HLA antigen complexes on cell membranes and muster specific cytotoxic T-lymphocyte responses (6, 7), and they augment natural killer cell activity (8). They further direct the cytotoxic T-lymphocyte response by decreasing the resistance of virus-infected cells to such attack while increasing the threshold of uninfected cells to attack (9, 10).The role of interferon in recovery from viral infections has been documented in many in viuo studies. Interferon has been shown to limit virus spread from focal sites of infection (ll), shorten the period of viremia and decrease the severity of acute systemic infection (12). Since interferon is ordinarily not detected in the serum of normal individuals, the finding of levels of interferon up to several hundred units per milliliter in serum of patients with a variety of viral infections also supports its role in acute viral infection (13).