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Human Coronavirus Infection Reorganizes Spatial Genomic Architecture in Permissive Lung Cells
Ankush Singhal1, Cullen Roth2, Sofiya N Micheva-Viteva3
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos,NM, USA.
Research Square
|April 1, 2024
Summary
Coronavirus infection alters lung cell 3D genome structure. 4DHiC simulations reveal chromatin restructuring, increased compactness, and altered gene accessibility, providing a mechanistic basis for observed gene expression changes.
Area of Science:
- Genomics
- Structural Biology
- Virology
Background:
- Understanding how viral infections impact host cell 3D genome organization is crucial for elucidating disease mechanisms.
- Chromatin conformation capture (Hi-C) and polymer simulations (4DHiC) offer powerful tools to study genome architecture.
Approach:
- Acquired Hi-C data from human fetal lung fibroblast (MRC5) cells infected with alpha-coronavirus 229E (CoV229E).
- Applied 4DHiC polymer simulations to reconstruct 3D genomic structures and dynamics from Hi-C maps.
- Analyzed viral-induced changes in genomic architecture over 48 hours post-infection.
Key Points:
- CoV229E infection induced substantial alterations in intra- and inter-chromosomal contacts.
- Simulations revealed increased chromatin compactness and A-B compartment mixing upon infection.
- Increased spatial accessibility to interferon-stimulated genes was observed early post-infection, followed by restructuring.
Conclusions:
- The study provides a mechanistic, structural basis for coronavirus-induced changes in lung cell chromosome architecture.
- Observed chromatin restructuring is consistent with suppressed gene expression following infection.
- 4DHiC is effective in modeling viral-induced 3D genome dynamics.
