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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Defective interfering particles: effects in modulating virus growth and persistence
1Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Abstract:
Defective interfering virus particles (DIP) frequently play an important part in viral persistence in vitro, and may in some instances modify a virus infection in vivo, causing attenuation or persistence of the infection. To explain certain aspects of the growth of these mutants in vitro, other factors have been invoked such as interferon, mutations in the wild-type virus or the infected cells, or other substances released by infected cells that attenuate the infection. We present here a simple model of the growth of DIP in vitro which shows that (a) the observed population dynamics of DIP can readily be explained without invoking such extrinsic factors; (b) the initial multiplicity of infection of DIP is the principal determinant of the outcome of infection in both single- and repeated-passage cultures; and (c) in a long-term culture in vitro, the criterion used to decide the time of virus passage directly determines how long the standard virus, DIP, and cells survive. This model may be used with minor modifications to predict the behavior in vitro of other mutant viruses with a dominantly interfering phenotype.
Insights
Defective interfering particles (DIPs) dynamics in vitro are explained by a simple model. Initial infection levels of DIPs and passage timing critically determine virus and cell survival, without needing external factors.
Area of Science:
- Virology
- Cell Biology
- Mathematical Modeling
Background:
- Defective interfering particles (DIPs) are known to influence viral infections in vitro and in vivo.
- Previous explanations for DIPs' behavior in vitro invoked external factors like interferon or cell mutations.
- A need exists for a simplified model to understand DIPs' population dynamics.
Purpose of the Study:
- To present a simple model explaining the in vitro growth dynamics of defective interfering particles (DIPs).
- To demonstrate that DIPs' population dynamics can be understood without invoking extrinsic factors.
- To identify key determinants of DIPs' infection outcomes in vitro.
Main Methods:
- Development of a mathematical model for DIP growth dynamics.
- Analysis of DIP population dynamics under varying initial multiplicities of infection.
- Simulation of long-term in vitro cultures with different virus passage criteria.
Main Results:
- The model successfully explains observed DIP population dynamics without external factors.
- Initial multiplicity of infection is the primary factor influencing infection outcomes in vitro.
- The timing of virus passage in long-term cultures dictates the survival of standard virus, DIPs, and host cells.
Conclusions:
- A simple model adequately describes DIPs' in vitro growth and population dynamics.
- Extrinsic factors are not necessary to explain DIPs' behavior in cell cultures.
- The model provides a framework for predicting the in vitro behavior of other interfering viral mutants.
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