Liang Weizheng, Xiao Jiajia, Zhu Zhenpeng, Wang Peng, Zheng Chunfu
Hebei Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.
Hebei North University, Zhangjiakou City, Hebei Province, China.
Methods Mol Biol. 2025;2940:43-61. doi: 10.1007/978-1-0716-4615-1_6.
Upon invasion of host cells, viruses trigger a wide range of changes in the host genome, including alterations in chromatin conformation, gene expression regulation, DNA methylation, and histone modification. These genomic changes not only contribute to viral replication and latency but also may promote disease onset and progression by interfering with the host immune response. The profound impact of viral infection on the host genome has become an important area of current virology research. With the continuous advancements in genomics, 3D genome technology has become a powerful tool for revealing chromatin folding and interactions in three dimensions. In virology, 3D genomic technology can be used to determine how viruses regulate host gene expression by altering the conformation of the host chromatin, which in turn drives viral infections and related diseases. In recent years, Hi-C technology, a high-resolution 3D genome analysis method, has revealed how viruses integrate into host chromatin by capturing spatial contacts in three dimensions, providing insights into how these interactions affect the viral lifecycle, latent state, and host immune response. In a SARS-CoV-2 study, Hi-C technology revealed the interactions between the virus and specific regions of the host genome and elucidated how these interactions dynamically regulate the viral replication process and the modulation of the host immune response. By capturing spatial contacts at high resolution, Hi-C technology provides a unique molecular perspective for the study of viral infection mechanisms and promotes the further development of virology research. This chapter focuses on the basic principles of 3D genome technology and its application in virology, with a particular emphasis on the innovative use of Hi-C technology in the study of viruses such as SARS-CoV-2, especially its important contributions to understanding viral integration sites and chromatin recombination mechanisms. This chapter will also elaborate on the Hi-C experimental steps, required materials, and data analysis process, providing researchers with clear operational guidelines and assisting in the in-depth exploration of viral infection mechanisms.
病毒侵入宿主细胞后，会引发宿主基因组的一系列广泛变化，包括染色质构象改变、基因表达调控、DNA甲基化和组蛋白修饰。这些基因组变化不仅有助于病毒复制和潜伏，还可能通过干扰宿主免疫反应促进疾病的发生和发展。病毒感染对宿主基因组的深远影响已成为当前病毒学研究的一个重要领域。随着基因组学的不断进步，三维基因组技术已成为揭示染色质三维折叠和相互作用的有力工具。在病毒学中，三维基因组技术可用于确定病毒如何通过改变宿主染色质构象来调节宿主基因表达，进而推动病毒感染和相关疾病的发生。近年来，Hi-C技术作为一种高分辨率的三维基因组分析方法，通过捕捉三维空间接触揭示了病毒如何整合到宿主染色质中，为了解这些相互作用如何影响病毒生命周期、潜伏状态和宿主免疫反应提供了见解。在一项关于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的研究中，Hi-C技术揭示了病毒与宿主基因组特定区域之间的相互作用，并阐明了这些相互作用如何动态调节病毒复制过程和宿主免疫反应的调节。通过高分辨率捕捉空间接触，Hi-C技术为病毒感染机制的研究提供了独特的分子视角，促进了病毒学研究的进一步发展。本章重点介绍三维基因组技术的基本原理及其在病毒学中的应用，特别强调Hi-C技术在SARS-CoV-2等病毒研究中的创新性应用，尤其是其对理解病毒整合位点和染色质重组机制的重要贡献。本章还将详细阐述Hi-C实验步骤、所需材料和数据分析过程，为研究人员提供清晰的操作指南，协助深入探索病毒感染机制。
