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Durso-Cain, K.* ; Kumberger, P.* ; Schälte, Y. ; Fink, T.* ; Dahari, H.* ; Hasenauer, J. ; Uprichard, S.L.* ; Graw, F.*

HCV spread kinetics reveal varying contributions of transmission modes to infection dynamics.

Viruses 13:1308 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1999-4915
e-ISSN 1999-4915
Journal Viruses
Quellenangaben Volume: 13, Issue: 7, Pages: , Article Number: 1308 Supplement: ,
Publisher MDPI
Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-553800-001
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)
DOI 10.3390/v13071308
WOS ID WOS:000677048300001
Scopus ID 85110614725
PubMed ID 34372514
Erfassungsdatum 2021-08-02
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