Utilization of Host Cell Chromosome Conformation by Viral Pathogens: Knowing When to Hold and When to Fold

Kinjal Majumder,Abigail J Morales

doi:10.3389/fimmu.2021.633762

Abstract

Though viruses have their own genomes, many depend on the nuclear environment of their hosts for replication and survival. A substantial body of work has therefore been devoted to understanding how viral and eukaryotic genomes interact. Recent advances in chromosome conformation capture technologies have provided unprecedented opportunities to visualize how mammalian genomes are organized and, by extension, how packaging of nuclear DNA impacts cellular processes. Recent studies have indicated that some viruses, upon entry into host cell nuclei, produce factors that alter host chromatin topology, and thus, impact the 3D organization of the host genome. Additionally, a variety of distinct viruses utilize host genome architectural factors to advance various aspects of their life cycles. Indeed, human gammaherpesviruses, known for establishing long-term reservoirs of latent infection in B lymphocytes, utilize 3D principles of genome folding to package their DNA and establish latency in host cells. This manipulation of host epigenetic machinery by latent viral genomes is etiologically linked to the onset of B cell oncogenesis. Small DNA viruses, by contrast, are tethered to distinct cellular sites that support virus expression and replication. Here, we briefly review the recent findings on how viruses and host genomes spatially communicate, and how this impacts virus-induced pathology.

Highlights

The advent of chromosome conformation capture (3C) technologies has provided unprecedented insights into the mechanisms by which cellular DNA is spooled and packaged into the nuclear microenvironment, and how this packaging impacts biological processes (Figure 1)
Emerging studies have focused on unraveling how viral pathogens utilize the principles of genome folding to navigate the nuclear environment and establish infection
We highlight the ability of a diverse array of DNA viruses to utilize genome-organizing protein CCCTCBinding Factor (CTCF) in one or both of two ways: 1. to impact the chromatin topology of the host genome or 2. to organize its own genome in ways that enable sophisticated epigenetic control (Figure 1)

Summary

Introduction

The advent of chromosome conformation capture (3C) technologies has provided unprecedented insights into the mechanisms by which cellular DNA is spooled and packaged into the nuclear microenvironment, and how this packaging impacts biological processes (Figure 1). The large 150 kb genome of HSV forms multiple DNA loops, not unlike TADs in the host cells, which are maintained by CTCF-bound elements and are essential for viral infection, latency and reactivation [38, 39].

Results

Conclusion