The Experts below are selected from a list of 236817 Experts worldwide ranked by ideXlab platform
Raul Andino - One of the best experts on this subject based on the ideXlab platform.
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RNA Virus population diversity an optimum for maximal fitness and virulence
Journal of Biological Chemistry, 2014Co-Authors: Victoria K Korboukh, Jamie J Arnold, Cheri A Lee, Ashley Acevedo, Marco Vignuzzi, Yinghong Xiao, Stephen Hemperly, Jason D Graci, Avery August, Raul AndinoAbstract:The ability of an RNA Virus to exist as a population of genetically distinct variants permits the Virus to overcome events during infections that would otherwise limit Virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a polioVirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2–3-fold that manifested in a 2–3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA Virus genome.
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the role of mutational robustness in RNA Virus evolution
Nature Reviews Microbiology, 2013Co-Authors: Adam S Lauring, Judith Frydman, Raul AndinoAbstract:RNA Viruses face dynamic environments and are masters at adaptation. During their short 'lifespans', they must surmount multiple physical, anatomical and immunological challenges. Central to their adaptative capacity is the enormous genetic diversity that characterizes RNA Virus populations. Although genetic diversity increases the rate of adaptive evolution, low replication fidelity can present a risk because excess mutations can lead to population extinction. In this Review, we discuss the strategies used by RNA Viruses to deal with the increased mutational load and consider how this mutational robustness might influence viral evolution and pathogenesis.
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codon usage determines the mutational robustness evolutionary capacity and virulence of an RNA Virus
Cell Host & Microbe, 2012Co-Authors: Adam S Lauring, Ashley Acevedo, Samantha B Cooper, Raul AndinoAbstract:Summary RNA Viruses exist as dynamic and diverse populations shaped by constant mutation and selection. Yet little is known about how the mutant spectrum contributes to Virus evolvability and pathogenesis. Because several codon choices are available for a given amino acid, a central question concerns whether viral sequences have evolved to optimize not only the protein coding consensus, but also the DNA/RNA sequences accessible through mutation. Here we directly test this hypothesis by comparing wild-type polioVirus to synthetic Viruses carrying re-engineered capsid sequences with hundreds of synonymous mutations. Strikingly, such rewiring of the population's mutant network reduced its robustness and attenuated the Virus in an animal model of infection. We conclude that the position of a Virus in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenicity. This organizing principle for RNA Virus populations confers tolerance to mutations and facilitates replication and spread within the dynamic host environment.
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implications of high RNA Virus mutation rates lethal mutagenesis and the antiviral drug ribavirin
Microbes and Infection, 2002Co-Authors: Shane Crotty, Raul AndinoAbstract:Abstract The antiviral drug ribavirin exhibits strong antiviral activity against a broad range of RNA Viruses. This drug is currently used clinically to treat hepatitis C Virus infections, respiratory syncytial Virus infections, and Lassa fever Virus infections. Although ribavirin was discovered in 1972, its mechanism of action has remained unclear until recently. Using polioVirus as an RNA Virus model, it was shown that ribavirin is a Virus mutagen, and it was proposed that the primary mechanism of action of ribavirin is via lethal mutagenesis of the RNA Virus genomes. This represents a novel antiviral mechanism of action and provides a model for the development of new antiviral strategies. In this review we discuss the genetic explanations, evolutionary implications, and drug development opportunities associated with RNA Virus mutagenesis.
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RNA Virus error catastrophe: Direct molecular test by using ribavirin
Proceedings of the National Academy of Sciences, 2001Co-Authors: Shane Crotty, C. E. Cameron, Raul AndinoAbstract:RNA Viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA Virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA Viruses may be susceptible to error catastrophe, where they undergo a sharp drop in viability after a modest increase in mutation frequency. We recently showed that the important broad-spectrum antiviral drug ribavirin (currently used to treat hepatitis C Virus infections, among others) is an RNA Virus mutagen, and we proposed that ribavirin's antiviral effect is by forcing RNA Viruses into error catastrophe. However, a direct demonstration of error catastrophe has not been made for ribavirin or any RNA Virus mutagen. Here we describe a direct demonstration of error catastrophe by using ribavirin as the mutagen and polioVirus as a model RNA Virus. We demonstrate that ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. A 99.3% loss in viral genome infectivity is observed after a single round of Virus infection in ribavirin concentrations sufficient to cause a 9.7-fold increase in mutagenesis. Compiling data on both the mutation levels and the specific infectivities of polioVirus genomes produced in the presence of ribavirin, we have constructed a graph of error catastrophe showing that normal polioVirus indeed exists at the edge of viability. These data suggest that RNA Virus mutagens may represent a promising new class of antiviral drugs.
Bryony C. Bonning - One of the best experts on this subject based on the ideXlab platform.
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Diabrotica undecimpunctata Virus 2, a Novel Small RNA Virus Discovered from Southern Corn Rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae).
Microbiology resource announcements, 2020Co-Authors: Sijun Liu, Arnubio Valencia-jiménez, Molly Darlington, Ana María Vélez, Bryony C. BonningAbstract:The genome of Diabrotica undecimpunctata Virus 2 (DuV2), a putative positive-sense, single-stranded RNA Virus identified from the southern corn rootworm transcriptome, comprises 5,313 nucleotides, including a short poly(A) tail. The two open reading frames encode a nonstructural polyprotein (p156) and a putative capsid protein (p25).
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genome sequence of a novel positive sense single stranded RNA Virus isolated from western corn rootworm diabrotica virgifera virgifera leconte
Genome Announcements, 2017Co-Authors: Sijun Liu, Yuting Chen, Thomas W Sappington, Bryony C. BonningAbstract:ABSTRACT The genome sequence of a novel small RNA Virus was assembled from the transcriptome of the western corn rootworm, Diabrotica virgifera virgifera. The assembled genome has 13,182 nucleotides with a 3′ polyadenylated tail. Two open reading frames are predicted to encode polyproteins of 2,838 and 1,073 amino acids.
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genome sequence of diabrotica virgifera virgifera Virus2 a novel small RNA Virus of the western corn rootworm diabrotica virgifera virgifera leconte
Genome Announcements, 2017Co-Authors: Sijun Liu, Yuting Chen, Thomas W Sappington, Bryony C. BonningAbstract:ABSTRACT The genome of a novel small RNA Virus, tentatively named Diabrotica virgifera virgifera Virus 2 (DvvV2), was identified in the western corn rootworm, Diabrotica virgifera virgifera LeConte, through transcriptome sequencing and confirmed by reverse transcription-PCR. Here, we report the near-complete nucleotide sequence and the genome organization of DvvV2.
Sijun Liu - One of the best experts on this subject based on the ideXlab platform.
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Diabrotica undecimpunctata Virus 2, a Novel Small RNA Virus Discovered from Southern Corn Rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae).
Microbiology resource announcements, 2020Co-Authors: Sijun Liu, Arnubio Valencia-jiménez, Molly Darlington, Ana María Vélez, Bryony C. BonningAbstract:The genome of Diabrotica undecimpunctata Virus 2 (DuV2), a putative positive-sense, single-stranded RNA Virus identified from the southern corn rootworm transcriptome, comprises 5,313 nucleotides, including a short poly(A) tail. The two open reading frames encode a nonstructural polyprotein (p156) and a putative capsid protein (p25).
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genome sequence of a novel positive sense single stranded RNA Virus isolated from western corn rootworm diabrotica virgifera virgifera leconte
Genome Announcements, 2017Co-Authors: Sijun Liu, Yuting Chen, Thomas W Sappington, Bryony C. BonningAbstract:ABSTRACT The genome sequence of a novel small RNA Virus was assembled from the transcriptome of the western corn rootworm, Diabrotica virgifera virgifera. The assembled genome has 13,182 nucleotides with a 3′ polyadenylated tail. Two open reading frames are predicted to encode polyproteins of 2,838 and 1,073 amino acids.
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genome sequence of diabrotica virgifera virgifera Virus2 a novel small RNA Virus of the western corn rootworm diabrotica virgifera virgifera leconte
Genome Announcements, 2017Co-Authors: Sijun Liu, Yuting Chen, Thomas W Sappington, Bryony C. BonningAbstract:ABSTRACT The genome of a novel small RNA Virus, tentatively named Diabrotica virgifera virgifera Virus 2 (DvvV2), was identified in the western corn rootworm, Diabrotica virgifera virgifera LeConte, through transcriptome sequencing and confirmed by reverse transcription-PCR. Here, we report the near-complete nucleotide sequence and the genome organization of DvvV2.
Bonning, Bryony C. - One of the best experts on this subject based on the ideXlab platform.
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Diabrotica undecimpunctata Virus 2, a Novel Small RNA Virus Discovered from Southern Corn Rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae)
DigitalCommons@University of Nebraska - Lincoln, 2020Co-Authors: Liu Sijun, Valencia-jiménez Arnubio, Darlington Molly, Vélez, Ana M., Bonning, Bryony C.Abstract:The genome of Diabrotica undecimpunctata Virus 2 (DuV2), a positive-sense, single-stranded RNA Virus identified from the southern corn root- worm transcriptome, comprises 5,313 nucleotides, including a short poly(A) tail. The two open reading frames encode a nonstructural polyprotein (p156) and a putative capsid protein (p25)
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Genome Sequence of a Small RNA Virus of the Southern Corn Rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae)
DigitalCommons@University of Nebraska - Lincoln, 2020Co-Authors: Liu Sijun, Valencia-jiménez Arnubio, Darlington Molly, Vélez, Ana M., Bonning, Bryony C.Abstract:The genome sequence of a novel small RNA Virus, tentatively named Diabrotica undecimpunctata Virus 1 (DuV1), was discovered from the transcriptome of the southern corn rootworm, Diabrotica undecimpunctata howardi Barber. DuV1 has a positive-sense, single-stranded RNA genome that encodes a single polyprotein of 3,401 amino acids with limited similarity to other Viruses
Jay D Evans - One of the best experts on this subject based on the ideXlab platform.
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development of a honey bee RNA Virus vector based on the genome of a deformed wing Virus
Viruses, 2020Co-Authors: Eugene V Ryabov, Krisztina Christmon, Matthew C Heerman, Francisco Posadaflorez, Robert L Harrison, Yanping Chen, Jay D EvansAbstract:We developed a honey bee RNA-Virus vector based on the genome of a picoRNA-like Deformed wing Virus (DWV), the main viral pathogen of the honey bee (Apis mellifera). To test the potential of DWV to be utilized as a vector, the 717 nt sequence coding for the enhanced green fluorescent protein (eGFP), flanked by the peptides targeted by viral protease, was inserted into an infectious cDNA clone of DWV in-frame between the leader protein and the Virus structural protein VP2 genes. The in vitro RNA transcripts from egfp-tagged DWV cDNA clones were infectious when injected into honey bee pupae. Stable DWV particles containing genomic RNA of the recovered DWV with egfp inserts were produced, as evidenced by cesium chloride density gradient centrifugation. These particles were infectious to honey bee pupae when injected intra-abdominally. Fluorescent microscopy showed GFP expression in the infected cells and Western blot analysis demonstrated accumulation of free eGFP rather than its fusions with DWV leader protein (LP) and/or viral protein (VP) 2. Analysis of the progeny egfp-tagged DWV showed gradual accumulation of genome deletions for egfp, providing estimates for the rate of loss of a non-essential gene an insect RNA Virus genome during natural infection.
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development of a honey bee RNA Virus vector based on the genome of deformed wing Virus
2020Co-Authors: Eugene V Ryabov, Krisztina Christmon, Matthew C Heerman, Francisco Posadaflorez, Robert L Harrison, Yanping Chen, Jay D EvansAbstract:We developed a honey bee RNA-Virus vector based on the genome of a picoRNA-like Deformed wing Virus (DWV), the main viral pathogen of the honey bee (Apis mellifera). To test the potential of DWV to be utilized as a vector, the 717 nt sequence coding for the enhanced green fluorescent protein (eGFP), flanked by the peptides targeted by viral protease, was inserted into an infectious cDNA clone of DWV in-frame between the leader protein and the Virus structural protein VP2 genes. The in vitro RNA transcripts from egfp-tagged DWV cDNA clones were infectious when injected into honey bee pupae. Stable DWV particles containing genomic RNA of the recovered DWV with egfp inserts were produced, as evidenced by cesium chloride density gradient centrifugation. These particles were infectious to honey bee pupae when injected intra-abdominally. Fluorescent microscopy showed GFP expression in the infected cells and Western blot analysis demonstrated accumulation of free eGFP rather than its fusions with DWV LP and/or VP2 proteins. Analysis of the progeny egfp-tagged DWV showed gradual accumulation of genome deletions for egfp, providing estimates for the rate of loss of a non-essential gene an insect RNA Virus genome during natural infection.
