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Single-Cell Analysis Uncovers Extensive Biological Noise in Poliovirus Replication
- Source :
- Journal of virology, vol 88, iss 11
- Publication Year :
- 2014
- Publisher :
- American Society for Microbiology, 2014.
-
Abstract
- Viral infections often begin with a very small number of initiating particles. Accordingly, the outcome of an infection is likely to be affected by variability in the initial molecular interactions between virus and host. In this study, we investigated the range of outcomes upon infection of single cells. We isolated individual cells infected with poliovirus at low or high multiplicities of infection (MOI) and measured viral genomic replication and infectious viral progeny in each cell. We first determined that at 7 h postinfection, the ratio of positive to negative strands in individual cells varies from 5:1 to more than 190:1, with and average of 20:1, suggesting a significant variability in RNA synthesis. We further found that while virus genome production is higher in cells infected at a high multiplicity, the production of infectious particles is largely independent of the number of viruses infecting each cell. Strikingly, by correlating RNA and particle production within individual infections, we uncovered a significant contribution of stochastic noise to the outcome of infection. At low MOI, stochastic influences appear as kinetic effects which are most critical at the initial steps in infection. At high MOI, stochastic influences appear to dictate the virus's ability to harness cellular resources. We conclude that biological noise is a critical determinant of the overall productivity of viral infections. The distinct nature of stochasticity in the outcome of infection by low and high numbers of viral particles may have important implications for our understanding of the determinants of successful viral infections. IMPORTANCE By correlating genome and particle production in single-cell infections, we elucidated sources of noise in viral infections. When a cell was infected by only a single infectious particle, variation in the kinetics of the initial steps of replication contributed significantly to the overall productivity of the infection. Additionally, variation in the distribution of subcellular resources impacted infections initiated by one or many infectious particles. We also observed that when a cell was infected with multiple particles, more genomes were produced, while particle production was hindered by an apparent cellular resource limit. Understanding variations in viral infections may illuminate the dynamics of infection and pathogenesis and has implications for virus adaptation and evolution.
- Subjects :
- Time Factors
viruses
Viral pathogenesis
Signal-To-Noise Ratio
Virus Replication
medicine.disease_cause
Medical and Health Sciences
Single-cell analysis
Models
2.1 Biological and endogenous factors
2.2 Factors relating to the physical environment
Viral
Aetiology
Genome
Reverse Transcriptase Polymerase Chain Reaction
Poliovirus
Biological Sciences
Genome Replication and Regulation of Viral Gene Expression
Infectious Diseases
Cytogenetic Analysis
Host-Pathogen Interactions
Single-Cell Analysis
Infection
Virus Integration
Immunology
Genome, Viral
Biology
Models, Biological
Microbiology
Virus
Viral entry
Virology
Genetics
medicine
Humans
DNA Primers
Stochastic Processes
Agricultural and Veterinary Sciences
Human Genome
RNA
Biological
Kinetics
Emerging Infectious Diseases
Good Health and Well Being
Viral replication
Hela Cells
Insect Science
HeLa Cells
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....b529bf8a16609d90900dc139bbe36aa9