Virome-wide analysis of histone modification mimicry motifs carried by viral proteins

Yang Xiao; Shuofeng Yuan; Ye Qiu; Xing-Yi Ge

doi:10.1016/j.virs.2024.09.004

October 2024

. doi: 10.1016/j.virs.2024.09.004

Citation: Yang Xiao, Shuofeng Yuan, Ye Qiu, Xing-Yi Ge. Virome-wide analysis of histone modification mimicry motifs carried by viral proteins .VIROLOGICA SINICA, 2024, 39(5) : 793-801. http://dx.doi.org/10.1016/j.virs.2024.09.004

病毒蛋白所携带的组蛋白修饰模拟序列的病毒组学分析

肖杨 ^a ,
袁硕峰 ^b ,
邱烨 ^a,, ,
葛行义 ^a,,

cstr: 32224.14.j.virs.2024.09.004

a. 湖南大学病原生物学与免疫学学院, 湖南省医学病毒学重点实验室, 长沙;
b. 香港大学李嘉诚医学院, 微生物学系, 香港特别行政区

通讯作者： 邱烨, qiuye@hnu.edu.cn; 葛行义, xyge@hnu.edu.cn
收稿日期： 2023-04-16
录用日期： 2024-09-11

摘要

组蛋白模拟（Histone mimicry, HM）指的是病毒蛋白中存在短线性序列，能模拟宿主组蛋白关键区域。这些序列有潜力干扰宿主细胞表观基因组,并拮抗宿主抗病毒反应。最新研究显示，HM对流感病毒和冠状病毒的致病性和传播性至关重要。然而，真核病毒中HM的分布、特征和功能仍不清楚。我们开发了一种生物信息学工具HiScan，用于识别病毒蛋白中的HM序列，并预测它们的功能。通过分析592643个病毒蛋白，我们发现，潜在的HM序列广泛分布于大部分病毒蛋白中。在动物病毒中，DNA病毒和RNA病毒中的HM序列数量比约为1.9:1，基因组更小的病毒具有更高的HM序列密度。值得注意的是，冠状病毒HM序列的分布不均匀，β冠状病毒（包括大部分对人类有致病性的冠状病毒）在NSP3、S和N蛋白中含有更多HM序列。综上所述，我们利用HiScan对病毒组进行的HM序列筛查，揭示了潜在HM序列在大部分病毒蛋白中广泛存在但分布不均匀，特别是在DNA病毒中分布较RNA病毒多。病毒HM可能在调节病毒致病性和病毒-宿主相互作用中发挥重要作用，这为病毒学和抗病毒药物研究提供了新的视角。
- 组蛋白模拟
- , 病毒蛋白
- , 组蛋白修饰
- , 进化
- , 冠状病毒

Virome-wide analysis of histone modification mimicry motifs carried by viral proteins

Yang Xiao ^a ,
Shuofeng Yuan ^b ,
Ye Qiu ^a,, ,
Xing-Yi Ge ^a,,

a. Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, Changsha, 410012, China;
b. Department of Microbiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, 999077, China

Corresponding author: Ye Qiu, qiuye@hnu.edu.cn Xing-Yi Ge, xyge@hnu.edu.cn
Received Date: 16 April 2023
Accepted Date: 11 September 2024

Abstract

Histone mimicry (HM) refers to the presence of short linear motifs in viral proteins that mimic critical regions of host histone proteins. These motifs have the potential to interfere with host cell epigenome and counteract antiviral response. Recent research shows that HM is critical for the pathogenesis and transmissibility of influenza virus and coronavirus. However, the distribution, characteristics, and functions of HM in eukaryotic viruses remain obscure. Herein, we developed a bioinformatic pipeline, Histone Motif Scan (HiScan), to identify HM motifs in viral proteins and predict their functions in silico. By analyzing 592,643 viral proteins using HiScan, we found that putative HM motifs were widely distributed in most viral proteins. Among animal viruses, the ratio of HM motifs between DNA viruses and RNA viruses was approximately 1.9:1, and viruses with smaller genomes had a higher density of HM motifs. Notably, coronaviruses exhibited an uneven distribution of HM motifs, with betacoronaviruses (including most human pathogenic coronaviruses) harboring more HM motifs than other coronaviruses, primarily in the NSP3, S, and N proteins. In summary, our virome-wide screening of HM motifs using HiScan revealed extensive but uneven distribution of HM motifs in most viral proteins, with a preference in DNA viruses. Viral HM may play an important role in modulating viral pathogenicity and virus-host interactions, making it an attractive area of research in virology and antiviral medication.
- Histone mimicry
- , Viral proteins
- , Histone modification
- , Evolution
- , Coronavirus

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