Genomic and template RNA transcription in a model of persistent enteroviral infection

Jw, Gow; Wm, Behan; Cash, Phillip; Simpson, K.; Po, Behan

doi:10.3109/13550289709015796

Cited by 6 publications

(8 citation statements)

References 46 publications

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“…The mechanisms by which enteroviruses persist are incompletely understood. Viral clearance is highly dependent on the production of antiviral antibody, and persistence of infectious virus is generally observed only in immunocompromised hosts such as patients with agammaglobulinemia (30) or during in vitro infection of certain primary cell cultures or cell lines (10,12,13,18,29). Single-stranded RNA viruses such as enteroviruses evolve rapidly due to high error rates and lack of a DNA template for use in correcting mismatches (22).…”

mentioning

confidence: 99%

Molecular Mechanisms of Coxsackievirus Persistence in Chronic Inflammatory Myopathy: Viral RNA Persists through Formation of a Double-Stranded Complex without Associated Genomic Mutations or Evolution

Tam

Messner

1999

J Virol

112

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Enterovirus infection and persistence have been implicated in the pathogenesis of certain chronic muscle diseases. In vitro studies suggest that persistent enteroviruses mutate, evolving into forms that are less lytic and display altered tropism, but it is less clear whether these mechanisms operate in vivo. In this study, persistent coxsackievirus RNA from the muscle of mice afflicted with chronic inflammatory myopathy (CIM) was characterized and compared with RNA from a virus that had established a persistent infection of G8 mouse myoblasts for 30 passages in vitro. Competitive strand-specific reverse transcription-PCR and susceptibility to RNase I treatment revealed that plus- and minus-strand viral RNAs were present at nearly equivalent levels in muscle and that they persisted in a double-stranded conformation. All regions of the viral genome persisted and were amplified as a series of seven overlapping fragments. Restriction endonuclease fingerprinting coupled with sequencing indicated that there was no evolution of the viral genome associated with its persistence in muscle. This contrasted with the productive persistent infection that was established in myoblast cultures, where plus-strand RNA predominated and persistent virus developed distinct mutations. In vitro persistence proceeded by a carrier culture mechanism and was completely dependent on production of infectious virus, since persistent viral RNA was not detected in cultures subjected to antibody-mediated curing. These experiments demonstrate that persistence of coxsackievirus RNA in muscle is not facilitated by distinct genetic changes in the virus that give rise to replication-defective forms but occurs primarily through production of stable double-stranded RNA that is produced as the acute viral infection resolves. The data suggest a mechanism for coxsackievirus persistence in myofibers and perhaps other nondividing cells whereby cells that survive infection could harbor persistent viral RNA for extended times without producing detectable levels of infectious virus.

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confidence: 99%

Molecular Mechanisms of Coxsackievirus Persistence in Chronic Inflammatory Myopathy: Viral RNA Persists through Formation of a Double-Stranded Complex without Associated Genomic Mutations or Evolution

Tam

Messner

1999

J Virol

112

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“…Our results implied that it was a primary impairment of mitochondria in skeletal muscles of mice with VMC. It was reported that viral RNA can be detected in skeletal muscle cells in patients with dilated cardiomyopathy [7] and in mice with VMC [2] , suggesting that the pathogenesis of the damage of mitochondria in skeletal muscle cells in VMC was same as that in cardiac muscle cells, and might be the direct damage by virus itself and the immunological damage evoked by the viral infection.…”

Section: Discussionmentioning

confidence: 97%

“…But the difficulty in obtaining biopsy samples of cardiac muscles restricts the study of VMC. Recently, it was reported that viral particles were detected in both cardiac and skeletal muscle cells in mice with VMC, accompanied with ultrastructural changes of skeletal muscle cells [2] . But it is unknown whether cardiac mitochondria are also injured in VMC, whether the impairments of mitochondria are observed simultaneously in skeletal muscles, whether the skeletal muscle cells can be used as a peripheral "window" to reflect cardiac mitochondrial impairment.…”

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confidence: 99%

Impairment of myocardial and skeletal mitochondria in mice with viral myocarditis and their correlation

Wei

Gao

Niu

et al. 2007

J. Huazhong Univ. Sc. Technol.

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In order to investigate the impairment of mitochondrial membrane phospholipid localization and DNA(3867) (mtDNA(3867)) deletion and the correlation between cardiac and skeletal muscle cells in mice with viral myocarditis, 50 BALB/c mice were divided into two groups randomly. In experimental group (n=40), the mice were intraperitoneally injected with 0.1 mL Eagle liquid with CVB3(TCID50=10(8)), while in the control group (n=10), the mice were subjected to equal volume of Eagle liquid. The impairment of mitochondrial membrane phospholipid localization and mtDNA(3867) deletion rate of cardiac and skeletal muscle were detected separately at day 3, 11 and 24 after injection. The correlation of mitochondrial membrane phospholipid localization and mtDNA(3867) deletion rate between cardiac and skeletal muscle cells cells was analyzed using Spearman method. At the day 3 after injection, in both cardiac and skeletal muscle cells, mtDNA(3867) deletion rate was significantly higher in experimental group than in control group (P<0.05), but the localization of mitochondrial membrane phospholipid showed no difference between two groups (P>0.05). At day 11 after injection, the mtDNA(3867) deletion rate of both cells in experimental group was increased to the peak level (P<0.05), and the impairment of mitochondrial membrane phospholipid localization of both cells also increased markedly in experimental group as compared with control group (P>0.05). At the day 24 after injection, the impairment of mitochondrial membrane phospholipid localization and mtDNA(3867) deletion of both cells showed a recovery tendency, but still severer than those at the day 3 after injection (P<0.05). The impairment of mitochondrial membrane phospholipid localization and mtDNA(3867) deletion were consistent and synchronistic between cardiac and skeletal muscle cells, and showed good correlations (P<0.05). The impairment of mitochondria plays an important role in the pathogenesis of viral myocarditis, and the skeletal muscle cells might act as a peripheral "window" to reflect the mitochondrial damage of cardiac myocytes.

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“…Evidence from coxsackie virus in human skeletal muscle cells does not support this position (Gow et al, 1997).…”

Section: Discussionmentioning

confidence: 98%

Levels of selection in positive-strand virus dynamics

Krakauer

Komarova

2003

Journal of Evolutionary Biology

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Conflicting selection pressures occurring over the life cycle of an organism constitute serious challenges to the robustness of replication. Viruses present a credible model system for analysing problems that arise through evolutionary conflicts of interest. We present a multi-level selection model for the life cycle of positive-strand RNA viruses. The model combines within-cell replication kinetics and protein synthesis, and between-cell population dynamics of virion production and transmission. We show how these two levels of within-host selection interact to produce tradeoffs in the life history strategy of a virus without consideration of host mortality. We find that viruses evolve towards intermediate rather than maximum encapsidation rates. This can be interpreted as selection for intermediate virulence through cellular persistence. We characterize a theoretical persistence threshold arising from the trade-off between genome replication and genetic translation within the cell. We present counter-intuitive relationships whereby increasing genome decay rates and rates of encapsidation lead to increases in the abundance of virusencoded proteins. Data from poliovirus suggest that viruses might be unable to resolve the vertical conflicts of interests among different levels of selection.

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Genomic and template RNA transcription in a model of persistent enteroviral infection

Cited by 6 publications

References 46 publications

Molecular Mechanisms of Coxsackievirus Persistence in Chronic Inflammatory Myopathy: Viral RNA Persists through Formation of a Double-Stranded Complex without Associated Genomic Mutations or Evolution

Molecular Mechanisms of Coxsackievirus Persistence in Chronic Inflammatory Myopathy: Viral RNA Persists through Formation of a Double-Stranded Complex without Associated Genomic Mutations or Evolution

Impairment of myocardial and skeletal mitochondria in mice with viral myocarditis and their correlation

Levels of selection in positive-strand virus dynamics

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