title: HIV-1 IN/Pol recruits LEDGF/p75 into viral particles.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Belete Ayele
authors: BA
authors: Desimmie
authors: Caroline
authors: C
authors: Weydert
authors: Rik
authors: R
authors: Schrijvers
authors: Sofie
authors: S
authors: Vets
authors: Jonas
authors: J
authors: Demeulemeester
authors: Paul
authors: P
authors: Proost
authors: Igor
authors: I
authors: Paron
authors: Jan
authors: J
authors: De Rijck
authors: Jan
authors: J
authors: Mast
authors: Norbert
authors: N
authors: Bannert
authors: Rik
authors: R
authors: Gijsbers
authors: Frauke
authors: F
authors: Christ
authors: Zeger
authors: Z
authors: Debyser
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D059748:Proteolysis; D014157:Transcription Factors / Q000378:metabolism*; D016662:Virus Integration; D014779:Virus Replication; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C504649:PSIP1 protein, human; D014157:Transcription Factors; D054302:pol Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1