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HCV Spread Kinetics Reveal Varying Contributions of Transmission Modes to Infection Dynamics

1
Department of Microbiology and Immunology, and The Infectious Disease and Immunology Research Institute, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA
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The Program for Experimental and Theoretical Modeling, Department of Medicine, Division of Hepatology, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA
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BioQuant-Center for Quantitative Biology, BIOMS, Heidelberg University, 69120 Heidelberg, Germany
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Mathematical Modeling of Biological Systems, Department of Mathematics, TU München, 85748 Garching, Germany
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Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany
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Faculty of Mathematics and Natural Sciences, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
These authors contributed equally.
Academic Editor: Rod Russell
Viruses 2021, 13(7), 1308; https://doi.org/10.3390/v13071308
Received: 20 May 2021 / Revised: 13 June 2021 / Accepted: 29 June 2021 / Published: 6 July 2021
(This article belongs to the Section Human Virology and Viral Diseases)
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. View Full-Text
Keywords: HCV; cell-to-cell transmission; mathematical modeling; spatial spread; agent-based model HCV; cell-to-cell transmission; mathematical modeling; spatial spread; agent-based model
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MDPI and ACS Style

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 2021, 13, 1308. https://doi.org/10.3390/v13071308

AMA Style

Durso-Cain K, Kumberger P, Schälte Y, Fink T, Dahari H, Hasenauer J, Uprichard SL, Graw F. HCV Spread Kinetics Reveal Varying Contributions of Transmission Modes to Infection Dynamics. Viruses. 2021; 13(7):1308. https://doi.org/10.3390/v13071308

Chicago/Turabian Style

Durso-Cain, Karina, Peter Kumberger, Yannik Schälte, Theresa Fink, Harel Dahari, Jan Hasenauer, Susan L. Uprichard, and Frederik Graw. 2021. "HCV Spread Kinetics Reveal Varying Contributions of Transmission Modes to Infection Dynamics" Viruses 13, no. 7: 1308. https://doi.org/10.3390/v13071308

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