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2010-06-02Zeitschriftenartikel DOI: 10.1128/JVI.02624-09
Mutations in the M112/M113-coding region facilitate murine cytomegalovirus replication in human cells.
dc.contributor.authorSchumacher, Uwe
dc.contributor.authorHandke, Wiebke
dc.contributor.authorJurak, Igor
dc.contributor.authorBrune, Wolfram
dc.date.accessioned2018-05-07T14:55:13Z
dc.date.available2018-05-07T14:55:13Z
dc.date.created2011-10-25
dc.date.issued2010-06-02none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reVfg44uqhGnw/PDF/28TaHvBCBSw.pdf
dc.identifier.urihttp://edoc.rki.de/176904/977
dc.description.abstractCytomegaloviruses, representatives of the Betaherpesvirinae, cause opportunistic infections in immunocompromised hosts. They infect various cells and tissues in their natural host but are highly species specific. For instance, human cytomegalovirus (HCMV) does not replicate in mouse cells, and human cells are not permissive for murine cytomegalovirus (MCMV) infection. However, the underlying molecular mechanisms are so far poorly understood. In the present study we isolated and characterized a spontaneously occurring MCMV mutant that has gained the capacity to replicate rapidly and to high titers in human cells. Compared to the parental wild-type (wt) virus, this mutant formed larger nuclear replication compartments and replicated viral DNA more efficiently. It also disrupted promyelocytic leukemia (PML) protein nuclear domains with greater efficiency but caused less apoptosis than did wt MCMV. Sequence analysis of the mutant virus genome revealed mutations in the M112/M113-coding region. This region is homologous to the HCMV UL112-113 region and encodes the viral early 1 (E1) proteins, which are known to play an important role in viral DNA replication. By introducing the M112/M113 mutations into wt MCMV, we demonstrated that they are sufficient to facilitate MCMV replication in human cells and are, at least in part, responsible for the efficient replication capability of the spontaneously adapted virus. However, additional mutations probably contribute as well. These results reveal a previously unrecognized role of the viral E1 proteins in regulating viral replication in different cells and provide new insights into the mechanisms of the species specificity of cytomegaloviruses.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectAnimalseng
dc.subjectHumanseng
dc.subjectMiceeng
dc.subjectVirus Replicationeng
dc.subjectMutationeng
dc.subjectViral Loadeng
dc.subjectMuromegalovirus/geneticseng
dc.subjectImmediate-Early Proteins/geneticseng
dc.subjectSequence Analysis DNAeng
dc.subjectDNA Viral/geneticseng
dc.subjectCells Culturedeng
dc.subjectAntigens Viral/geneticseng
dc.subjectCell Survivaleng
dc.subjectDNA Mutational Analysis DNA Viral/chemistryeng
dc.subjectMuromegalovirus/growth & developmenteng
dc.subjectMissenseeng
dc.subject.ddc610 Medizin
dc.titleMutations in the M112/M113-coding region facilitate murine cytomegalovirus replication in human cells.
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10015823
dc.identifier.doi10.1128/JVI.02624-09
dc.identifier.doihttp://dx.doi.org/10.25646/902
local.edoc.container-titleJournal of Virology
local.edoc.container-textSchumacher, U., Handke, W., Jurak, I., Brune, W. Mutations in the M112/M113-coding region facilitate murine cytomegalovirus replication in human cells (2010) Journal of Virology, 84 (16), pp. 7994-8006.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://jvi.asm.org/cgi/content/short/84/16/7994
local.edoc.container-publisher-nameAmerican Society for Microbiology
local.edoc.container-volume84
local.edoc.container-issue16
local.edoc.container-year2010

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