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2018-01-29Zeitschriftenartikel DOI: 10.1038/s41598-018-20130-9
Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores
dc.contributor.authorGrossegesse, Marica
dc.contributor.authorDoellinger, Joerg
dc.contributor.authorFritsch, Annemarie
dc.contributor.authorLaue, Michael
dc.contributor.authorPiesker, Janett
dc.contributor.authorSchaade, Lars
dc.contributor.authorNitsche, Andreas
dc.date.accessioned2018-05-07T20:54:55Z
dc.date.available2018-05-07T20:54:55Z
dc.date.created2018-01-29
dc.date.issued2018-01-29none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/recLmMlRIRjZs/PDF/27Nchh4rRG1zs.pdf
dc.identifier.urihttp://edoc.rki.de/176904/2928
dc.description.abstractThe emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown. Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins. Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly. However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins. Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Biologische Sicherheit
dc.subject.ddc610 Medizin
dc.titleGlobal ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10056850
dc.identifier.doi10.1038/s41598-018-20130-9
dc.identifier.doihttp://dx.doi.org/10.25646/2853
local.edoc.container-titleScientific Reports
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.nature.com/articles/s41598-018-20130-9
local.edoc.container-publisher-nameNature Publishing Group
local.edoc.container-volume8
local.edoc.container-issue1807
local.edoc.container-year2018

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