Reoviruses

Coombs, Kevin M.

doi:10.1002/9780470015902.a0001084.pub3

Cited by 3 publications

(3 citation statements)

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“…Reoviruses are routinely cultured and titrated in mouse L929 cells [ 22 , 23 ]. The virus also is capable of growing in HeLa cells [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…The Ortheoreoviruses include nonfusogenic MRV and fusogenic avian reovirus. The Reoviridae family also contains rotaviruses [ 25 ], orbiviruses [ 26 ], and at least 9 other genera, several of which can infect animals, insects and/or plants [ 23 , 24 ]. MRV infections are generally mild in humans but many of the other family members are highly pathogenic in their hosts.…”

Section: Introductionmentioning

confidence: 99%

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HeLa cell response proteome alterations induced by mammalian reovirus T3D infection

Coombs

2013

Virol J

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BackgroundCells are exposed to multiple stressors that induce significant alterations in signaling pathways and in the cellular state. As obligate parasites, all viruses require host cell material and machinery for replication. Virus infection is a major stressor leading to numerous induced modifications. Previous gene array studies have measured infected cellular transcriptomes. More recently, mass spectrometry-based quantitative and comparative assays have been used to complement such studies by examining virus-induced alterations in the cellular proteome.MethodsWe used SILAC (stable isotope labeling with amino acids in cell culture), a non-biased quantitative proteomic labeling technique, combined with 2-D HPLC/mass spectrometry and reciprocal labeling to identify and measure relative quantitative differences in HeLa cell proteins in purified cytosolic and nuclear fractions after reovirus serotype 3 Dearing infection. Protein regulation was determined by z-score analysis of each protein’s label distribution.ResultsA total of 2856 cellular proteins were identified in cytosolic fractions by 2 or more peptides at >99% confidence and 884 proteins were identified in nuclear fractions. Gene ontology analyses indicated up-regulated host proteins were associated with defense responses, immune responses, macromolecular binding, regulation of immune effector processes, and responses to virus, whereas down-regulated proteins were involved in cell death, macromolecular catabolic processes, and tissue development.ConclusionsThese analyses identified numerous host proteins significantly affected by reovirus T3D infection. These proteins map to numerous inflammatory and innate immune pathways, and provide the starting point for more detailed kinetic studies and delineation of virus-modulated host signaling pathways.

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“…Reoviruses are routinely cultured and titrated in mouse L929 cells [ 22 , 23 ]. The virus also is capable of growing in HeLa cells [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HeLa cell response proteome alterations induced by mammalian reovirus T3D infection

Coombs

2013

Virol J

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“…First, resolution of reovirus genomic 154 dsRNA segments using SDS-PAGE was used to determine if gross changes could be observed among the 10 155 reovirus genome segments. Reovirus serotypes 1, 2, and 3 produce unique electrophenotype (Coombs, 2011; 156 Shatkin et al, 1968), but even independent isolates of reovirus from the same serotype commonly show mobility 157 differences (Hrdy et al, 1979). T3D PL , T3D KC and T3D TD electrophenotypes were indistinguishable, although 158 very distinct from serotype 1 Lang (T1L) and serotype 2 Jones (T2J) prototypes ( Figure 1G), suggesting close 159…”

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confidence: 99%

Genetic Polymorphisms and Molecular Mechanisms Mediating Oncolytic Potency of Reovirus Strains

Mohamed

Clements

Konda

et al. 2019

Preprint

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18The Dearing strain of Mammalian orthoreovirus (T3D) is undergoing clinical trials as an oncolytic 19 virotherapeutic agent. In this study, a comprehensive phenotypic and genetic comparison of T3D virus stocks 20 from various laboratories and commercial sources revealed that T3D laboratory strains differ substantially in their 21 oncolytic activities in vitro and in vivo. Superior replication of the most-oncolytic T3D lab strain was attributed to 22 virus will impact the immune-stimulatory landscape (e.g. cytokines), by interacting with specific cellular 64 signaling pathways. To test these predictions, we explored the relationships between oncolytic activity and virus 65 genetic and phenotypic features, among various highly related laboratory strains of T3D. 66In this study, we discovered that highly related laboratory strains of T3D exhibit significant differences in 67 oncolytic potency in vitro and in vivo. These findings reinforce that virus genomic and phenotypic features have a 68 strong impact on oncolytic proficiencies. Since the T3D strains were highly genetically related, they provided an 69 opportunity to discover novel determinants of reovirus oncolysis. A comprehensive genetic and phenotypic 70 comparison of T3D laboratory strains revealed that the most-oncolytic strain (obtained from the Patrick Lee 71 laboratory, T3D PL ) has 3 distinct and additive advantages over the less-oncolytic strains (obtained from the 72 Terence Dermody and Kevin Coombs laboratories, T3D TD and T3D KC , respectively). Relative to T3D TD and 73 T3D KC , T3D PL exhibited superior replication in transformed cells in a single round of infection, and induced less 74 IFN signaling which facilitated enhanced cell-cell spread. The genes that contribute to enhanced replication and 75 spread of T3D PL were then characterized, and found to be (1) the T3D PL S1-encoded σ1, which increased the 76 proportion of virions that harbour sufficient number of σ1 trimers for binding to cells, (2) T3D PL S4-encoded σ3, 77 which increased expression of NF-κB stimulated genes, (3) the M1-encoded µ2, which increased virus 78 transcription and filamentous factories, and (4) the L3-encoded λ1, which increased virus factory size. When 79 evaluating which specific polymorphisms in S4, M1, and L3 contribute to oncolysis, surprisingly specific amino 80 acid differences between T3D PL versus T3D TD had both positive and negative contributions, and ultimately a 81 hybrid between T3D PL and T3D TD exhibited superior oncolytic activity even relative to T3D PL . This finding 82 suggests that the T3D oncolytic vector may benefit from continued genetic development to fully thrive in tumors. 83Finally, important to the current excitement surrounding the immunotherapeutic value of oncolytic viruses, was 84 our discovery that T3D laboratory strains induced expression of different cytokines by infected tumor cells. 85Specifically, while T3D PL caused high induction of NF-κB-dependent cytokines but low induction of IFN-86 dependent cytokines, the reciprocal was tr...

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Comparative proteomic analyses demonstrate enhanced interferon and STAT-1 activation in reovirus T3D-infected HeLa cells

Ezzati

Komher

Severini

et al. 2015

Front. Cell. Infect. Microbiol.

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As obligate intracellular parasites, viruses are exclusively and intimately dependent upon their host cells for replication. During replication viruses induce profound changes within cells, including: induction of signaling pathways, morphological changes, and cell death. Many such cellular perturbations have been analyzed at the transcriptomic level by gene arrays and recent efforts have begun to analyze cellular proteomic responses. We recently described comparative stable isotopic (SILAC) analyses of reovirus, strain type 3 Dearing (T3D)-infected HeLa cells. For the present study we employed the complementary labeling strategy of iTRAQ (isobaric tags for relative and absolute quantitation) to examine HeLa cell changes induced by T3D, another reovirus strain, type 1 Lang, and UV-inactivated T3D (UV-T3D). Triplicate replicates of cytosolic and nuclear fractions identified a total of 2375 proteins, of which 50, 57, and 46 were significantly up-regulated, and 37, 26, and 44 were significantly down-regulated by T1L, T3D, and UV-T3D, respectively. Several pathways, most notably the Interferon signaling pathway and the EIF2 and ILK signaling pathways, were induced by virus infection. Western blots confirmed that cells were more strongly activated by live T3D as demonstrated by elevated levels of key proteins like STAT-1, ISG-15, IFIT-1, IFIT-3, and Mx1. This study expands our understanding of reovirus-induced host responses.

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Reoviruses

Cited by 3 publications

References 30 publications

HeLa cell response proteome alterations induced by mammalian reovirus T3D infection

HeLa cell response proteome alterations induced by mammalian reovirus T3D infection

Genetic Polymorphisms and Molecular Mechanisms Mediating Oncolytic Potency of Reovirus Strains

Comparative proteomic analyses demonstrate enhanced interferon and STAT-1 activation in reovirus T3D-infected HeLa cells

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