Viral Mimicry of Cdc2/cyclin-dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress

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Viral Mimicry of Cdc2/cyclin-dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress

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dc.contributor.author Hamirally, Sofia
dc.contributor.author Kamil, Jeremy P.
dc.contributor.author Ndassa-Colday, Yasmine M.
dc.contributor.author Jahng, Wan Jin
dc.contributor.author Baek, Moon-Chang
dc.contributor.author Noton, Sarah
dc.contributor.author Silva, Laurie A.
dc.contributor.author Simpson-Holley, Martha
dc.contributor.author Lin, Alison J.
dc.contributor.author Knipe, David Mahan
dc.contributor.author Golan, David Eric
dc.contributor.author Marto, Jarrod
dc.contributor.author Coen, Donald Mark
dc.date.accessioned 2011-03-28T03:12:36Z
dc.date.issued 2009
dc.identifier.citation Hamirally, Sofia, Jeremy P. Kamil, Yasmine M. Ndassa-Colday, Alison J. Lin, Wan Jin Jahng, Moon-Chang Baek, Sarah Noton, Laurie A. Silva, Martha Simpson-Holley, David M. Knipe, David E. Golan, Jarrod A. Marto, and Donald M. Coen. 2009. Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress. PLoS Pathogens 5(1). en_US
dc.identifier.issn 1553-7366 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4774202
dc.description.abstract The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser[super]22). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser[super]22 is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.ppat.1000275 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625439/pdf/ en_US
dash.license LAA
dc.subject biochemistry en_US
dc.subject molecular biology en_US
dc.subject virology en_US
dc.subject biophysics en_US
dc.subject protein chemistry and proteomics en_US
dc.subject cell biology en_US
dc.subject nuclear structure and function en_US
dc.subject infectious diseases en_US
dc.subject viral infections en_US
dc.subject antivirals, including modes of action and resistance en_US
dc.subject new therapies, including antivirals and immunotherapy en_US
dc.subject virion structure, assembly, and egress en_US
dc.title Viral Mimicry of Cdc2/cyclin-dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Pathogens en_US
dash.depositing.author Lin, Alison J.
dc.date.available 2011-03-28T03:12:36Z
dash.affiliation.other HMS^Microbiology and Molecular Genetics en_US
dash.affiliation.other HMS^Biological Chemistry and Molecular Pharmacology en_US
dash.affiliation.other HMS^Biological Chemistry and Molecular Pharmacology en_US

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