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dc.contributor.authorJacque, Jean-Marc
dc.contributor.authorMann, Angela
dc.contributor.authorEnslen, Herve
dc.contributor.authorSharova, Natalia
dc.contributor.authorBrichacek, Beda
dc.contributor.authorDavis, Roger J.
dc.contributor.authorStevenson, Mario
dc.date2022-08-11T08:10:02.000
dc.date.accessioned2022-08-23T16:52:47Z
dc.date.available2022-08-23T16:52:47Z
dc.date.issued1998-06-20
dc.date.submitted2008-07-09
dc.identifier.citation<p>EMBO J. 1998 May 1;17(9):2607-18. <a href="http://dx.doi.org/10.1093/emboj/17.9.2607">Link to article on publisher's site</a></p>
dc.identifier.issn0261-4189 (Print)
dc.identifier.doi10.1093/emboj/17.9.2607
dc.identifier.pmid9564043
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42125
dc.description.abstractInfection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity. Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity. These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9564043&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170602/
dc.subjectAntigens, CD4
dc.subjectCalcium-Calmodulin-Dependent Protein Kinases
dc.subjectCell Line
dc.subjectCell Membrane
dc.subjectCell Nucleus
dc.subjectHIV Reverse Transcriptase
dc.subjectHIV-1
dc.subjectHela Cells
dc.subjectHumans
dc.subjectKidney
dc.subjectKinetics
dc.subjectMAP Kinase Kinase 1
dc.subject*Mitogen-Activated Protein Kinase Kinases
dc.subjectPolymerase Chain Reaction
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProtein-Tyrosine Kinases
dc.subjectRecombinant Fusion Proteins
dc.subjectTetradecanoylphorbol Acetate
dc.subjectTransfection
dc.subjectVirion
dc.subjectVirus Replication
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleModulation of HIV-1 infectivity by MAPK, a virion-associated kinase
dc.typeJournal Article
dc.source.journaltitleThe EMBO journal
dc.source.volume17
dc.source.issue9
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/500
dc.identifier.contextkey544982
html.description.abstract<p>Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity. Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity. These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway.</p>
dc.identifier.submissionpathoapubs/500
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages2607-18


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