title: Nucleocytoplasmic shuttling of HIV-1 integrase is controlled by the viral Rev protein.
abstract: In the current study we show that the Rev protein of Human Immunodeficiency Virus type 1 (HIV-1) inhibits nuclear import and mediates nuclear export of the HIV-1 integrase (IN) protein, which catalyzes integration of the viral cDNA. Interaction between IN and Rev in virus infected cells, resulting in the formation of a Rev-IN complex, has been previously described by us. Here we show that nuclear import of the IN, is inhibited by early expressed Rev. No nuclear import of IN was observed when Rev-overexpressing cells were infected by wild-type HIV-1. Similarly, no translocation of IN into nuclei was observed in the presence of Rev-derived peptides. On the other hand, massive nuclear import was observed following infection by a ΔRev virus or in the presence of peptides that promote dissociation of the Rev-IN complex. Our results show that IN is only transiently present within the nuclei of infected cells. Treatment of infected cells with leptomycin B caused nuclear retention of the Rev-IN complex. Removal of the leptomycin from these treated cells resulted in nuclear export of both Rev and IN. On the other hand, disruption of the nuclear located Rev-IN complex resulted in export of only the Rev protein indicating Rev-mediated nuclear export of IN. Our results suggest the involvement of Rev in regulating the integration process by limiting the number of integration events per cell despite the presence of numerous copies of viral cDNA.
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences.
authors.forename: Aviad
authors.initials: A
authors.lastname: Levin
authors.forename: Zvi
authors.initials: Z
authors.lastname: Hayouka
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.forename: Abraham
authors.initials: A
authors.lastname: Loyter
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D057809:HEK293 Cells; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D013997:Time Factors; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1