Human cytomegalovirus-induced host protein citrullination is crucial for viral replication.
Human cytomegalovirus-induced host protein citrullination is crucial for viral replication.
复制标题
人巨细胞病毒诱导的宿主蛋白瓜氨酸对病毒复制至关重要。
DOI：
10.1038/s41467-021-24178-6
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发表时间：
2021-06-23
影响因子：
16.6
通讯作者：
Landolfo S
中科院分区：
文献类型：
--
作者：
Griffante G;Gugliesi F;Pasquero S;Dell'Oste V;Biolatti M;Salinger AJ;Mondal S;Thompson PR;Weerapana E;Lebbink RJ;Soppe JA;Stamminger T;Girault V;Pichlmair A;Oroszlán G;Coen DM;De Andrea M;Landolfo S
瓜氨酸化是通过蛋白精氨酸脱亚胺酶（pad）将精氨酸转化为瓜氨酸的过程，其失调与各种类型的癌症和自身免疫性疾病的发病机制有关。与人类巨细胞病毒（HCMV）诱导细胞蛋白翻译后修饰以获得生存优势的能力一致，我们发现HCMV感染原代人成纤维细胞会触发pad介导的几种宿主蛋白的瓜氨酸化，并且这种活性促进病毒适应性。瓜氨酸组分析显示，细胞和病毒蛋白的去亚胺水平都发生了显著变化，干扰素（IFN）诱导蛋白IFIT1是去亚胺程度最高的蛋白之一。由于IFIT1基因缺失强烈促进HCMV生长，并且体外IFIT1瓜氨酸化会削弱其与5 ' -pp - rna结合的能力，我们提出病毒诱导的IFIT1瓜氨酸化是HCMV逃避宿主抗病毒抗性的机制之一。总的来说，我们的发现指出瓜氨酸化在破坏细胞对病毒感染的反应中起着至关重要的作用。瓜氨酸化是精氨酸的翻译后修饰。在这里，作者表明HCMV感染增加宿主和病毒蛋白的瓜氨酸化以促进感染，瓜氨酸化干扰素诱导蛋白IFIT1在RNA结合中受损，这是一种潜在的逃避机制。
Citrullination is the conversion of arginine-to-citrulline by protein arginine deiminases (PADs), whose dysregulation is implicated in the pathogenesis of various types of cancers and autoimmune diseases. Consistent with the ability of human cytomegalovirus (HCMV) to induce post-translational modifications of cellular proteins to gain a survival advantage, we show that HCMV infection of primary human fibroblasts triggers PAD-mediated citrullination of several host proteins, and that this activity promotes viral fitness. Citrullinome analysis reveals significant changes in deimination levels of both cellular and viral proteins, with interferon (IFN)-inducible protein IFIT1 being among the most heavily deiminated one. As genetic depletion of IFIT1 strongly enhances HCMV growth, and in vitro IFIT1 citrullination impairs its ability to bind to 5’-ppp-RNA, we propose that viral-induced IFIT1 citrullination is a mechanism of HCMV evasion from host antiviral resistance. Overall, our findings point to a crucial role of citrullination in subverting cellular responses to viral infection. Citrullination is a posttranslational modification of arginines. Here, the authors show that HCMV infection increases citrullination of host and virus proteins to promote infection and that citrullinated interferon-inducible protein IFIT1 is impaired in RNA binding, as a potential mechanism of evasion.
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影响因子：
3.7
作者：
Currie SM;Findlay EG;McHugh BJ;Mackellar A;Man T;Macmillan D;Wang H;Fitch PM;Schwarze J;Davidson DJ
通讯作者：
Davidson DJ
影响因子：
2.9
作者：
Bicker, Kevin L.;Thompson, Paul R.
通讯作者：
Thompson, Paul R.
DOI：
10.1073/pnas.1612444114
发表时间：
2017-03-14
影响因子：
11.1
作者：
Abbas, Yazan M.;Laudenbach, Beatrice Theres;Nagar, Bhushan
通讯作者：
Nagar, Bhushan
影响因子：
12.8
作者：
Acharya, Nimish K.;Nagele, Eric P.;Nagele, Robert G.
通讯作者：
Nagele, Robert G.
影响因子：
3.7
作者：
Barlow PG;Svoboda P;Mackellar A;Nash AA;York IA;Pohl J;Davidson DJ;Donis RO
通讯作者：
Donis RO