Integrated multiomics reveals host-virus coadaptation in persistent foot-and-mouth disease virus infection
Shuang Wang1, Zhihui Zhang1, Sumin Wei1
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
Abstract:
A comprehensive understanding of host-virus interactions during persistent foot-and-mouth disease virus (FMDV) infection is essential for elucidating the mechanisms that underpin disease causation by this highly contagious pathogen. This understanding necessitates the development of stable in vitro models. In this study, we established a model of persistent FMDV serotype O infection in Madin-Darby bovine kidney epithelial cells followed by integrated multiomics analyses. These analyses revealed that host cells adapt to persistent viral infection by reprogramming mitochondrial metabolism. This reprogramming is accompanied by alterations in mitochondrial structure and function, as well as the suppression of the apoptotic response in host cells. In particular, bystander cells, which are devoid of active viral replication, display enhanced proliferative capacity and possess a distinct microenvironmental signature that potentially increases viral susceptibility, facilitating sustained virus persistence within the cell population. Moreover, persistent viruses have evolved enhanced replicative fitness. Our findings elucidate the biological characteristics of FMDV-infected cell populations that persistently harbour the virus, reveal host-virus coadaptation, and highlight the critical role of bystander cells in sustaining persistent FMDV infection. These discoveries establish the foundation for further mechanistic studies of FMDV persistence maintenance.
Insights
Persistent foot-and-mouth disease virus (FMDV) infection involves host cell adaptation through mitochondrial reprogramming and altered apoptosis. Bystander cells play a key role in sustaining FMDV persistence.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Understanding persistent foot-and-mouth disease virus (FMDV) infection is crucial for controlling this highly contagious pathogen.
- Stable in vitro models are needed to study FMDV persistence mechanisms.
Purpose of the Study:
- To establish a model of persistent FMDV serotype O infection in bovine kidney cells.
- To investigate host cell adaptation and virus-host interactions during FMDV persistence using multiomics.
Main Methods:
- Establishment of a persistent FMDV serotype O infection model in Madin-Darby bovine kidney epithelial cells.
- Integrated multiomics analyses to study host cell responses.
Main Results:
- Host cells reprogram mitochondrial metabolism, altering mitochondrial structure and function.
- Suppression of host cell apoptosis and enhanced proliferation in bystander cells were observed.
- Persistent FMDV strains exhibit increased replicative fitness.
Conclusions:
- Host cells adapt to persistent FMDV infection via metabolic reprogramming and apoptosis suppression.
- Bystander cells with enhanced proliferative capacity contribute to sustained viral persistence.
- Host-virus coadaptation is critical for maintaining FMDV persistence.
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