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Published on: March 19, 2018
Inhibition of infection spread by co-transmitted defective interfering particles
Ashley Baltes1,2, Fulya Akpinar1,2, Bahar Inankur1,2
1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Abstract:
Although virus release from host cells and tissues propels the spread of many infectious diseases, most virus particles are not infectious; many are defective, lacking essential genetic information needed for replication. When defective and viable particles enter the same cell, the defective particles can multiply while interfering with viable particle production. Defective interfering particles (DIPs) occur in nature, but their role in disease pathogenesis and spread is not known. Here, we engineered an RNA virus and its DIPs to express different fluorescent reporters, and we observed how DIPs impact viral gene expression and infection spread. Across thousands of host cells, co-infected with infectious virus and DIPs, gene expression was highly variable, but average levels of viral reporter expression fell at higher DIP doses. In cell populations spatial patterns of infection spread provided the first direct evidence for the co-transmission of DIPs with infectious virus. Patterns of spread were highly sensitive to the behavior of initial or early co-infected cells, with slower overall spread stemming from higher early DIP doses. Under such conditions striking patterns of patchy gene expression reflected localized regions of DIP or virus enrichment. From a broader perspective, these results suggest DIPs contribute to the ecological and evolutionary persistence of viruses in nature.
Insights
Defective interfering particles (DIPs) can hinder infectious virus replication and spread. This study shows DIPs are co-transmitted with viruses, influencing infection patterns and potentially aiding viral persistence.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Most virus particles are not infectious, with many being defective and lacking replication capabilities.
- Defective interfering particles (DIPs) can interfere with the replication of viable viruses when co-infecting the same cell.
- The role of DIPs in disease pathogenesis and viral spread remains largely unknown.
Purpose of the Study:
- To investigate the impact of DIPs on viral gene expression and infection spread.
- To engineer an RNA virus and its DIPs with distinct fluorescent reporters for observation.
- To provide direct evidence for the co-transmission of DIPs with infectious viruses.
Main Methods:
- Engineered an RNA virus and its DIPs to express different fluorescent reporters.
- Co-infected host cells with infectious virus and engineered DIPs.
- Analyzed viral gene expression variability and spatial patterns of infection spread across cell populations.
Main Results:
- Viral gene expression showed high variability, with average reporter levels decreasing at higher DIP doses.
- Spatial patterns provided the first direct evidence for DIP co-transmission with infectious virus.
- Higher early DIP doses resulted in slower overall infection spread and patchy gene expression patterns.
Conclusions:
- DIPs influence viral gene expression and alter infection spread dynamics.
- Co-transmission of DIPs with infectious viruses occurs and impacts infection patterns.
- DIPs may contribute to the ecological and evolutionary persistence of viruses.
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