Evolutionarily conserved herpesviral protein interaction networks.
Evolutionarily conserved herpesviral protein interaction networks.
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DOI：
10.1371/journal.ppat.1000570
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发表时间：
2009-09
期刊：
影响因子：
6.7
通讯作者：
Haas J
中科院分区：
文献类型：
--
作者：
Fossum E;Friedel CC;Rajagopala SV;Titz B;Baiker A;Schmidt T;Kraus T;Stellberger T;Rutenberg C;Suthram S;Bandyopadhyay S;Rose D;von Brunn A;Uhlmann M;Zeretzke C;Dong YA;Boulet H;Koegl M;Bailer SM;Koszinowski U;Ideker T;Uetz P;Zimmer R;Haas J
疱疹病毒是一类广泛存在于脊椎动物中的DNA病毒，可引起多种疾病。它们具有范围从120至240 kbp的dsDNA基因组，编码70至170个开放阅读框。我们以前报道了两种疱疹病毒，水痘带状疱疹病毒（VZV）和卡波西肉瘤相关疱疹病毒（KSHV）的蛋白质相互作用网络。在这项研究中，我们系统地测试了另外三种疱疹病毒，单纯疱疹病毒1型（HSV-1），小鼠巨细胞病毒和EB病毒，蛋白质相互作用，以便能够进行比较分析的所有三个疱疹病毒亚科。我们通过全基因组酵母双杂交筛选（Y2 H）鉴定了735种相互作用，并与VZV和KSHV的相互作用组一起，在分析中包括总共1，007种病毒内蛋白质相互作用。虽然以前没有报道过大量的相互作用，但我们能够鉴定出一组高度保守的蛋白质相互作用的核心，如HSV-1 UL 33与核出口蛋白UL 31/UL 34之间的相互作用。尽管序列相似性普遍较低，但orthopathy蛋白之间的相互作用是保守的，这表明功能可能比序列更保守。通过结合不同物种的相互作用组，我们能够系统地解决Y2 H系统覆盖率低的问题，并提取出单一物种中不明显的生物相关相互作用。疱疹病毒蛋白在整个感染周期中以复杂的方式相互作用。这可能是最好的例子，在这个过程中，大量的病毒蛋白聚集在一起，形成新的病毒颗粒，随后从感染的细胞释放。更详细地了解病毒蛋白如何相互作用，可能有助于开发抑制这些相互作用并因此阻断病毒复制的药物。在这里，我们提出了三个全基因组的研究蛋白质-蛋白质相互作用的疱疹病毒单纯疱疹病毒I，鼠巨细胞病毒和EB病毒。我们总共在这三种病毒中发现了735种相互作用，其中大部分以前没有报道过。通过将这些研究与我们先前发表的卡波西肉瘤相关疱疹病毒和水痘带状疱疹病毒的研究相结合，我们能够对五种相关病毒物种的相互作用进行比较分析。我们观察到，高比例的相互作用是保守的不同物种之间，尽管低程度的序列保守性。这意味着通过比较相互作用数据，我们能够增加我们的病毒网络的覆盖范围，从而获得疱疹病毒蛋白之间相互作用的更好和更完整的图片。
Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species. Herpesvirus proteins interact with each other in a complex manner throughout the infectious cycle. This is probably best exemplified in the process where a large number of viral proteins come together to form new viral particles which are subsequently released from the infected cell. A more detailed understanding of how viral proteins interact with each other might assist the development of drugs which may inhibit these interactions and consequently block viral replication. Here we present three genome-wide studies of protein-protein interactions in the herpesviruses herpes simplex virus I, murine cytomegalovirus and Epstein-Barr virus. Altogether we identified 735 interactions in the three viruses, most of which have not previously been reported. By combining these studies with our previously published studies for Kaposi's sarcoma-associated herpesvirus and varicella-zoster virus we were able to perform a comparative analysis of interactions in five related viral species. We observed that a high proportion of interactions were conserved between the different species, despite a low degree of sequence conservation. This implies that by comparing interaction data, we were able to increase the coverage of our viral networks and thus obtain a better and more complete picture of interactions between herpesviral proteins.
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影响因子：
12.3
作者：
Hart GT;Ramani AK;Marcotte EM
通讯作者：
Marcotte EM
DOI：
10.1073/pnas.79.2.555
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CEBRIAN, J;KASCHKADIERICH, C;SHELDRICK, P
通讯作者：
SHELDRICK, P
影响因子：
5.4
作者：
Bubeck, A;Wagner, M;Koszinowski, UH
通讯作者：
Koszinowski, UH
影响因子：
5.4
作者：
Gonnella, R;Farina, A;Faggioni, A
通讯作者：
Faggioni, A
影响因子：
30.8
作者：
Bartel, PL;Roecklein, JA;Fields, S
通讯作者：
Fields, S