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Article: Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells

TitleInhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells
Authors
Issue Date1999
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 1999, v. 96 n. 21, p. 11860-11865 How to Cite?
AbstractPersistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA- dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1β converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K- AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-α synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.
Persistent Identifierhttp://hdl.handle.net/10722/170296
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYeung, MCen_US
dc.contributor.authorChang, DLen_US
dc.contributor.authorCamantigue, REen_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:18Z-
dc.date.available2012-10-30T06:07:18Z-
dc.date.issued1999en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1999, v. 96 n. 21, p. 11860-11865en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/170296-
dc.description.abstractPersistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA- dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1β converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K- AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-α synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshApoptosisen_US
dc.subject.meshCell Survivalen_US
dc.subject.meshCytopathogenic Effect, Viralen_US
dc.subject.meshEncephalomyocarditis Virus - Growth & Developmenten_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshHumansen_US
dc.subject.meshInterferons - Metabolismen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshRna, Antisense - Metabolismen_US
dc.subject.meshReoviridae - Growth & Developmenten_US
dc.subject.meshRespirovirus - Growth & Developmenten_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshU937 Cellsen_US
dc.subject.meshVirus Activationen_US
dc.subject.meshEif-2 Kinase - Physiologyen_US
dc.titleInhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cellsen_US
dc.typeArticleen_US
dc.identifier.emailLau, AS:asylau@hku.hken_US
dc.identifier.authorityLau, AS=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.96.21.11860en_US
dc.identifier.pmid10518541-
dc.identifier.scopuseid_2-s2.0-0032742095en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032742095&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume96en_US
dc.identifier.issue21en_US
dc.identifier.spage11860en_US
dc.identifier.epage11865en_US
dc.identifier.isiWOS:000083166800034-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYeung, MC=7101861664en_US
dc.identifier.scopusauthoridChang, DL=7403319393en_US
dc.identifier.scopusauthoridCamantigue, RE=6504330262en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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