Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins
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DOI：
10.1016/j.celrep.2019.04.063
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发表时间：
2019-05-14
期刊：
影响因子：
8.8
通讯作者：
Sauter, Daniel
中科院分区：
文献类型：
--
作者：
Braun, Elisabeth;Hotter, Dominik;Sauter, Daniel
鸟苷酸结合蛋白（GBP）5是一种干扰素（IFN）诱导的细胞因子，通过不完全理解的机制降低HIV-1感染性。在这里，我们表明，这种活动是由GBP 2共享，但不是由人类GBP家族的其他成员。GBP 2/5降低细胞前蛋白转化酶弗林蛋白酶的活性，弗林蛋白酶介导HIV-1包膜蛋白（Env）前体gp 160转化为成熟gp 120和gp 41。由于该过程引发HIV-1 Env进行膜融合，在GB 2/5存在下产生的病毒颗粒由于非功能性gp 160的掺入增加而感染性差。弗林蛋白酶活性对于许多病毒病原体的包膜糖蛋白的加工至关重要。同样，GBP 2/5还抑制寨卡、麻疹和甲型流感病毒复制，并降低携带马尔堡和小鼠白血病病毒糖蛋白的病毒颗粒的感染性。总的来说，我们的研究结果表明，GPB 2/5发挥广泛的抗病毒活性，通过抑制病毒依赖因子弗林蛋白酶的活性。
Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by an incompletely understood mechanism. Here, we show that this activity is shared by GBP2, but not by other members of the human GBP family. GBP2/5 decrease the activity of the cellular proprotein convertase furin, which mediates conversion of the HIV-1 envelope protein (Env) precursor gp160 into mature gp120 and gp41. Because this process primes HIV-1 Env for membrane fusion, viral particles produced in the presence of GB 2/5 are poorly infectious due to increased incorporation of non-functional gp160. Furin activity is critical for the processing of envelope glycoproteins of many viral pathogens. Consistently, GBP2/5 also inhibit Zika, measles, and influenza A virus replication and decrease infectivity of viral particles carrying glycoproteins of Marburg and murine leukemia viruses. Collectively, our results show that GPB2/5 exert broad antiviral activity by suppressing the activity of the virus-dependency factor furin.