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钱迪普拉病毒的基因组和结构洞察:印度和西非毒株的计算机模拟比较分析及潜在宿主受体相互作用

Genomic and Structural Insights into Chandipura Virus: A Comparative in Silico Analysis of Indian and West African Strains and Potential Host Receptor Interactions.

作者信息

Gupta Megha, Mallick Disharee, Kumar Dilip, Kumar Rajesh

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, Uttarakhand, India.

Trivedi School of Biosciences, Ashoka University, Sonipat, Haryana, India.

出版信息

Curr Microbiol. 2025 May 9;82(6):286. doi: 10.1007/s00284-025-04258-2.

DOI:10.1007/s00284-025-04258-2
PMID:40346308
Abstract

Chandipura virus (CHPV), a member of the Rhabdoviridae family, is an emerging pathogen responsible for encephalitis outbreaks, particularly among children under 15 years of age. Predominantly transmitted by sandflies, CHPV has caused multiple outbreaks in India, whereas strains from West African countries, including Kenya, Senegal, and Nigeria, have not been linked to human infections. The CHPV glycoprotein (G protein), a crucial spike protein, plays a key role in viral entry into host cells. In this study, we performed an in silico analysis to identify the potential mechanism of viral entry into host cells through interactions with the G protein. We also conducted bioinformatics analyses to examine the global distribution of CHPV strains and performed comparative structural and sequence-level analyses of the CHPV G protein. The phylogenetic analysis revealed a clear division of the CHPV G protein into two distinct clades. Despite this divergence, genome-wide analysis revealed high sequence conservation across the CHPV strains. Additionally, we identified potential interactions between the CHPV G protein and human receptors such as Lipoprotein Receptor-related Protein 1 (LRP1), facilitated by conserved lysine residues in the CHPV G protein in a calcium-dependent manner. The conservation of interacting residues across all strains raises concerns about the zoonotic potential of CHPV, particularly in regions where the virus is circulating in sandfly populations but has not yet caused any reported human infection. Our findings offer valuable insights into the genetic and structural similarities of CHPV strains, emphasizing the CHPV potential to spread beyond its current geographic boundaries and possibly cause human infections.

摘要

钱迪普拉病毒(CHPV)是弹状病毒科的成员,是一种新兴病原体,可引发脑炎疫情,尤其是在15岁以下儿童中。CHPV主要通过白蛉传播,在印度已引发多次疫情,而来自包括肯尼亚、塞内加尔和尼日利亚在内的西非国家的毒株尚未与人类感染相关联。CHPV糖蛋白(G蛋白)是一种关键的刺突蛋白,在病毒进入宿主细胞过程中起关键作用。在本研究中,我们进行了计算机模拟分析,以确定病毒通过与G蛋白相互作用进入宿主细胞的潜在机制。我们还进行了生物信息学分析,以研究CHPV毒株的全球分布,并对CHPV G蛋白进行了比较结构和序列水平分析。系统发育分析显示CHPV G蛋白明显分为两个不同的进化枝。尽管存在这种差异,但全基因组分析显示CHPV毒株之间具有高度的序列保守性。此外,我们确定了CHPV G蛋白与人类受体如脂蛋白受体相关蛋白1(LRP1)之间的潜在相互作用,这是由CHPV G蛋白中保守的赖氨酸残基以钙依赖方式促进的。所有毒株中相互作用残基的保守性引发了对CHPV人畜共患病潜力的担忧,特别是在病毒在白蛉种群中传播但尚未导致任何报告的人类感染的地区。我们的研究结果为CHPV毒株的遗传和结构相似性提供了有价值的见解,强调了CHPV有可能传播到其当前地理边界之外并可能导致人类感染。

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本文引用的文献

1
The evolving landscape of Chandipura virus: A comprehensive account of outbreaks to recent advances.钱德布尔病毒的演变态势:从疫情爆发到近期进展的全面阐述
Virology. 2025 Jul;608:110541. doi: 10.1016/j.virol.2025.110541. Epub 2025 Apr 15.
2
Phylogenetic Analysis of : Insights from a Preliminary Genomic Study.系统发育分析:来自初步基因组研究的见解
Int J Mol Sci. 2025 Jan 25;26(3):1021. doi: 10.3390/ijms26031021.
3
The Low-Density Lipoprotein Receptor-Related Protein-1 Is Essential for Dengue Virus Infection.低密度脂蛋白受体相关蛋白1对登革病毒感染至关重要。
Viruses. 2024 Oct 30;16(11):1692. doi: 10.3390/v16111692.
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Accurate structure prediction of biomolecular interactions with AlphaFold 3.利用 AlphaFold 3 进行生物分子相互作用的精确结构预测。
Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w. Epub 2024 May 8.
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Database resources of the National Center for Biotechnology Information.国家生物技术信息中心数据库资源。
Nucleic Acids Res. 2024 Jan 5;52(D1):D33-D43. doi: 10.1093/nar/gkad1044.
6
Host proteins Alpha-2-Macroglobulin and LRP1 associate with Chandipura virus.宿主蛋白 Alpha-2-巨球蛋白和 LRP1 与 Chandipura 病毒结合。
Biochimie. 2024 Mar;218:105-117. doi: 10.1016/j.biochi.2023.07.019. Epub 2023 Jul 28.
7
Diversity of sandflies in Vidarbha region of Maharashtra, India, a region endemic to Chandipura virus encephalitis.印度马哈拉施特拉邦维达巴地区(Vidarbha region)的白蛉多样性,该地区是昌迪普尔病毒脑炎的地方性疫区。
Indian J Med Res. 2023 Apr;157(4):259-267. doi: 10.4103/ijmr.IJMR_3974_20.
8
Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1.奥罗普切正布尼亚病毒感染是由细胞宿主因子 Lrp1 介导的。
Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2204706119. doi: 10.1073/pnas.2204706119. Epub 2022 Aug 8.
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Lrp1 is a host entry factor for Rift Valley fever virus.Lrp1 是裂谷热病毒的宿主进入因子。
Cell. 2021 Sep 30;184(20):5163-5178.e24. doi: 10.1016/j.cell.2021.09.001. Epub 2021 Sep 23.
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MEGA11: Molecular Evolutionary Genetics Analysis Version 11.MEGA11:分子进化遗传学分析版本 11。
Mol Biol Evol. 2021 Jun 25;38(7):3022-3027. doi: 10.1093/molbev/msab120.