Viral remodeling of the 4D nucleome

Exp Mol Med. 2024 Apr;56(4):799-808. doi: 10.1038/s12276-024-01207-0. Epub 2024 Apr 25.


The dynamic spatial organization of genomes across time, referred to as the four-dimensional nucleome (4DN), is a key component of gene regulation and biological fate. Viral infections can lead to a reconfiguration of viral and host genomes, impacting gene expression, replication, latency, and oncogenic transformation. This review provides a summary of recent research employing three-dimensional genomic methods such as Hi-C, 4C, ChIA-PET, and HiChIP in virology. We review how viruses induce changes in gene loop formation between regulatory elements, modify chromatin accessibility, and trigger shifts between A and B compartments in the host genome. We highlight the central role of cellular chromatin organizing factors, such as CTCF and cohesin, that reshape the 3D structure of both viral and cellular genomes. We consider how viral episomes, viral proteins, and viral integration sites can alter the host epigenome and how host cell type and conditions determine viral epigenomes. This review consolidates current knowledge of the diverse host-viral interactions that impact the 4DN.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Genome, Viral*
  • Host-Pathogen Interactions
  • Humans
  • Virus Diseases / metabolism
  • Virus Diseases / virology
  • Viruses / genetics
  • Viruses / metabolism


  • Chromatin