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

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 spr...

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Main Authors: Durso-Cain, Karina (Author) , Kumberger, Peter (Author) , Schälte, Yannik (Author) , Fink, Theresa (Author) , Dahari, Harel (Author) , Hasenauer, Jan (Author) , Uprichard, Susan L. (Author) , Graw, Frederik (Author)
Format: Article (Journal)
Language:English
Published: 6 July 2021
In: Viruses
Year: 2021, Volume: 13, Issue: 7, Pages: 1-22
ISSN:1999-4915
DOI:10.3390/v13071308
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v13071308
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/13/7/1308
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Author Notes:Karina Durso-Cain, Peter Kumberger, Yannik Schälte, Theresa Fink, Harel Dahari, Jan Hasenauer, Susan L. Uprichard and Frederik Graw
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Summary: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.
Item Description:Gesehen am 14.10.2021
Physical Description:Online Resource
ISSN:1999-4915
DOI:10.3390/v13071308