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HCV spread kinetics reveal varying contributions of transmission modes to infection dynamics.
Viruses 13:1308 (2021)
The hepatitis C virus (HCV) is capable of spreading within a host by two different transmission modes: cell-free and cell-to-cell. However, the contribution of each of these transmission mechanisms to HCV spread is unknown. To dissect the contribution of these different transmission modes to HCV spread, we measured HCV lifecycle kinetics and used an in vitro spread assay to monitor HCV spread kinetics after a low multiplicity of infection in the absence and presence of a neutralizing antibody that blocks cell-free spread. By analyzing these data with a spatially explicit mathematical model that describes viral spread on a single-cell level, we quantified the contribution of cell-free, and cell-to-cell spread to the overall infection dynamics and show that both transmission modes act synergistically to enhance the spread of infection. Thus, the simultaneous occurrence of both transmission modes represents an advantage for HCV that may contribute to viral persistence. Notably, the relative contribution of each viral transmission mode appeared to vary dependent on different experimental conditions and suggests that viral spread is optimized according to the environment. Together, our analyses provide insight into the spread dynamics of HCV and reveal how different transmission modes impact each other.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Agent-based Model ; Cell-to-cell Transmission ; Hcv ; Mathematical Modeling ; Spatial Spread; Hepatitis-c-virus; To-cell Spread; Replication; Multiscale; Inference; Host
ISSN (print) / ISBN
1999-4915
e-ISSN
1999-4915
Journal
Viruses
Quellenangaben
Volume: 13,
Issue: 7,
Article Number: 1308
Publisher
MDPI
Publishing Place
St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
FitMultiCell-project (Federal Ministry of Education and Research of Germany)
German Research Foundation (D.F.G.)
state of Baden-Wurttemberg through bwHPC (MLS-WISO)
NIH
U.S. National Institute of Health (NIH)
Chica and Heinz Schaller-Foundation
Center for Modeling and Simulation in the Biosciences (BIOMS)
German Research Foundation (D.F.G.)
state of Baden-Wurttemberg through bwHPC (MLS-WISO)
NIH
U.S. National Institute of Health (NIH)
Chica and Heinz Schaller-Foundation
Center for Modeling and Simulation in the Biosciences (BIOMS)