title: Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration.
abstract: BACKGROUND
  The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN), catalyzes the integration of viral DNA into the host cell genome. IN catalyzes the first step of the integration process, namely the 3'-end processing in which IN removes a pGT dinucleotide from the 3' end of each viral long terminal repeat (LTR). Following nuclear import of the viral preintegration complex, the host chromosomal DNA becomes accessible to the viral cDNA and the second step of the integration process, namely the strand-transfer step takes place. This ordered sequence of events, centered on integration, is mandatory for HIV replication.
  
  
  RESULTS
  Using an integrase peptide library, we selected two peptides, designated INr-1 and INr-2, which interact with the Rev protein and probably mediate the Rev-integrase interaction. Using an in-vitro assay system, we show that INr-1 and INr-2 are able to abrogate the inhibitory effects exerted by Rev and Rev-derived peptides on integrase activity. Both INr-1 and INr-2 were found to be cell-permeable and nontoxic, allowing a study of their effect in HIV-1-infected cultured cells. Interestingly, both INr peptides stimulated virus infectivity as estimated by production of the viral P24 protein, as well as by determination of the appearance of newly formed virus particles. Furthermore, kinetics studies revealed that the cell-permeable INr peptides enhance the integration process, as was indeed confirmed by direct determination of viral DNA integration by real-time PCR.
  
  
  CONCLUSIONS
  The results of the present study raise the possibility that in HIV-infected cells, the Rev protein may be involved in the integration of proviral DNA by controlling/regulating the activity of the integrase. Release from such inhibition leads to stimulation of IN activity and multiple viral DNA integration events.
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Aviad
authors.initials: A
authors.lastname: Levin
authors.forename: Zvi
authors.initials: Z
authors.lastname: Hayouka
authors.forename: Markus
authors.initials: M
authors.lastname: Helfer
authors.forename: Ruth
authors.initials: R
authors.lastname: Brack-Werner
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.forename: Abraham
authors.initials: A
authors.lastname: Loyter
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics*; D019427:HIV Integrase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D016662:Virus Integration; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D010455:Peptides; D054321:rev Gene Products, Human Immunodeficiency Virus; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1