Zur Kurzanzeige

2015-02-12Zeitschriftenartikel DOI: 10.1186/s12977-014-0134-4
HIV-1 IN/Pol recruits LEDGF/p75 into viral particles
dc.contributor.authorDesimmie, Belete Ayele
dc.contributor.authorWeydert, Caroline
dc.contributor.authorSchrijvers, Rik
dc.contributor.authorVets, Sofie
dc.contributor.authorDemeulemeester, Jonas
dc.contributor.authorProost, Paul
dc.contributor.authorParon, Igor
dc.contributor.authorRijck, Jan de
dc.contributor.authorMast, Jan
dc.contributor.authorBannert, Norbert
dc.contributor.authorGijsbers, Rik
dc.contributor.authorChrist, Frauke
dc.contributor.authorDebyser, Zeger
dc.date.accessioned2018-05-07T18:08:24Z
dc.date.available2018-05-07T18:08:24Z
dc.date.created2015-03-13
dc.date.issued2015-02-12none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/recPqAM8glZYY/PDF/24qxjWWbxdI.pdf
dc.identifier.urihttp://edoc.rki.de/176904/2028
dc.description.abstractBackground: The dynamic interaction between HIV and its host governs the replication of the virus and the study of the virus-host interplay is key to understand the viral lifecycle. The host factor lens epithelium-derived growth factor (LEDGF/p75) tethers the HIV preintegration complex to the chromatin through a direct interaction with integrase (IN). Small molecules that bind the LEDGF/p75 binding pocket of the HIV IN dimer (LEDGINs) block HIV replication through a multimodal mechanism impacting early and late stage replication including HIV maturation. Furthermore, LEDGF/p75 has been identified as a Pol interaction partner. This raised the question whether LEDGF/p75 besides acting as a molecular tether in the target cell, also affects late steps of HIV replication. Results: LEDGF/p75 is recruited into HIV-1 particles through direct interaction with the viral IN (or Pol polyprotein) and is a substrate for HIV-1 protease. Incubation in the presence of HIV-1 protease inhibitors resulted in detection of full-length LEDGF/p75 in purified viral particles. We also demonstrate that inhibition of LEDGF/p75-IN interaction by specific mutants or LEDGINs precludes incorporation of LEDGF/p75 in virions, underscoring the specificity of the uptake. LEDGF/p75 depletion did however not result in altered LEDGIN potency. Conclusion: Together, these results provide evidence for an IN/Pol mediated uptake of LEDGF/p75 in viral particles and a specific cleavage by HIV protease. Understanding of the possible role of LEDGF/p75 or its cleavage fragments in the viral particle awaits further experimentation.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectIntegraseeng
dc.subjectLEDGF/p75eng
dc.subjectProteaseeng
dc.subjectProtease cleavage siteseng
dc.subjectAssemblyeng
dc.subject.ddc610 Medizin
dc.titleHIV-1 IN/Pol recruits LEDGF/p75 into viral particles
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10038973
dc.identifier.doi10.1186/s12977-014-0134-4
dc.identifier.doihttp://dx.doi.org/10.25646/1953
local.edoc.container-titleRetrovirology
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.retrovirology.com/content/12/1/16
local.edoc.container-publisher-nameBioMedCentral
local.edoc.container-volume12
local.edoc.container-issue16
local.edoc.container-year2015

Zur Kurzanzeige