Search results for "Vesiculovirus"
showing 8 items of 8 documents
Collective Infection of Cells by Viral Aggregates Promotes Early Viral Proliferation and Reveals a Cellular-Level Allee Effect
2018
In addition to the conventional release of free, individual virions, virus dispersal can involve multi-virion assemblies that collectively infect cells. However, the implications of collective infection for viral fitness remain largely unexplored. Using vesicular stomatitis virus, here, we compare the fitness of free versus saliva-aggregated viral particles. We find that aggregation has a positive effect on early progeny production, conferring a fitness advantage relative to equal numbers of free particles in most cell types. The advantage of aggregation resides, at least partially, in increasing the cellular multiplicity of infection. In mouse embryonic fibroblasts, the per capita, short-t…
Multi-virion infectious units arise from free viral particles in an enveloped virus
2017
Many animal viruses are enveloped in a lipid bilayer uptaken from cellular membranes. Since viral surface proteins bind to these membranes to initiate infection, we hypothesized that free virions may also be capable of interacting with the envelopes of other virions extracellularly. Here, we demonstrate this hypothesis in the vesicular stomatitis virus (VSV), a prototypic negative-strand RNA virus composed by an internal ribonucleocapsid, a matrix protein, and an external envelope1. Using microscopy, dynamic light scattering, differential centrifugation, and flow cytometry, we show that free viral particles can spontaneously aggregate into multi-virion infectious units. We also show that, f…
Single-Cell Analysis of RNA Virus Infection Identifies Multiple Genetically Diverse Viral Genomes within Single Infectious Units
2015
Summary Genetic diversity enables a virus to colonize novel hosts, evade immunity, and evolve drug resistance. However, viral diversity is typically assessed at the population level. Given the existence of cell-to-cell variation, it is critical to understand viral genetic structure at the single-cell level. By combining single-cell isolation with ultra-deep sequencing, we characterized the genetic structure and diversity of a RNA virus shortly after single-cell bottlenecks. Full-length sequences from 881 viral plaques derived from 90 individual cells reveal that sequence variants pre-existing in different viral genomes can be co-transmitted within the same infectious unit to individual cell…
Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells
2014
Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specifi…
Collective Viral Spread Mediated by Virion Aggregates Promotes the Evolution of Defective Interfering Particles
2020
Recent insights have revealed that viruses use a highly diverse set of strategies to release multiple viral genomes into the same target cells, allowing the emergence of beneficial, but also detrimental, interactions among viruses inside infected cells. This has prompted interest among microbial ecologists and evolutionary biologists in studying how collective dispersal impacts the outcome of viral infections. Here, we have used vesicular stomatitis virus as a model system to study the evolutionary implications of collective dissemination mediated by viral aggregates, since this virus can spontaneously aggregate in the presence of saliva. We find that saliva-driven aggregation has a dual ef…
A genetic background with low mutational robustness is associated with increased adaptability to a novel host in an RNA virus.
2009
Although mutational robustness is central to many evolutionary processes, its relationship to evolvability remains poorly understood and has been very rarely tested experimentally. Here, we measure the evolvability of Vesicular stomatitis virus in two genetic backgrounds with different levels of mutational robustness. We passaged the viruses into a novel cell type to model a host-jump episode, quantified changes in infectivity and fitness in the new host, evaluated the cost of adaptation in the original host and analyzed the genetic basis of this adaptation. Lineages evolved from the less robust genetic background demonstrated increased adaptability, paid similar costs of adaptation to the …
Enhanced adaptation of vesicular stomatitis virus in cells infected with vaccinia virus.
2008
Infections involving different viruses (multiple infections) are common in nature and can take place between different strains of the same virus or between different virus species, including DNA and RNA viruses. The influence of multiple infections on viral evolution has been previously studied using different populations of the same virus. Here, we took a step forward by studying the evolution of an RNA virus (vesicular stomatitis virus, VSV) in the presence of a resident DNA virus (vaccinia virus, VV). Cell cultures were infected with a constant amount of VV, and VSV was added at four different post-VV-inoculation times and four different population sizes. The results showed that the pres…
Variation in RNA virus mutation rates across host cells.
2014
It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10−6 to 10−4 substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly…