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Updated: Jun 25, 2026

Assembly and Purification of Prototype Foamy Virus Intasomes
Published on: March 19, 2018
Multiple-hit inhibition of infection by defective interfering particles
Kristen A Stauffer Thompson1, Grzegorz A Rempala2, John Yin1
1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706-1607, USA.
Abstract:
Defective interfering particles (DIPs) are virus-like particles that arise during virus growth, fail to grow in the absence of virus, and replicate at the expense of virus during co-infections. The inhibitory effects of DIPs on virus growth are well established, but little is known about how DIPs influence their own growth. Here vesicular stomatitis virus (VSV) and its DIPs were used to co-infect BHK cells, and the effect of DIP dose on virus and DIP production was measured using a yield-reduction assay. The resulting dose-response data were used to fit and evaluate mathematical models that employed different assumptions. Our analysis supports a multiple-hit process where DIPs inhibit or promote virus and DIP production, depending on dose. Specifically, three regimes of co-infection were apparent: (i) low DIP - where both virus and DIPs are amplified, (ii) medium DIP - where amplification of both virus and DIPs is inhibited, and (iii) high DIP - with limited recovery of virus production and further inhibition of DIP growth. In addition, serial-passage infections enabled us to estimate the frequency of de novo DIP generation during virus amplification. Our combined experiments and models provide a means to understand better how DIPs quantitatively impact the growth of viruses and the spread of their infections.
Insights
Defective interfering particles (DIPs) impact virus growth differently based on their dose. Low doses amplify both virus and DIPs, while medium and high doses inhibit their replication.
Area of Science:
- Virology
- Molecular Biology
- Systems Biology
Background:
- Defective interfering particles (DIPs) are virus-derived entities that require helper virus for replication.
- While DIPs are known to inhibit viral growth, their own replication dynamics and dose-dependent effects are poorly understood.
Purpose of the Study:
- To investigate the quantitative impact of defective interfering particle (DIP) dose on both DIP and helper virus production during co-infection.
- To develop and evaluate mathematical models describing the complex interactions between viruses and DIPs.
Main Methods:
- Co-infection of BHK cells with vesicular stomatitis virus (VSV) and varying doses of VSV DIPs.
- Yield-reduction assays to quantify virus and DIP production.
- Mathematical modeling to analyze dose-response data and explore different mechanistic assumptions.
Main Results:
- Three distinct co-infection regimes were identified based on DIP dose: low DIP (amplification of both), medium DIP (inhibition of both), and high DIP (limited virus recovery, further DIP inhibition).
- DIPs exhibit a dose-dependent effect, inhibiting or promoting virus and DIP production.
- Serial passage experiments provided estimates for de novo DIP generation frequency.
Conclusions:
- DIPs play a complex, dose-dependent role in viral replication dynamics.
- Mathematical modeling is crucial for understanding the quantitative impact of DIPs on virus growth and infection spread.
- This study provides a framework for predicting DIP-virus interactions in various infection scenarios.
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