Cytoplasmic recruitment of INI1 and PML on incoming HIV preintegration complexes: interference with early steps of viral replication.
During the early phase of the retroviral life cycle, only a fraction of internalized virions end up integrating their genome into the chromosome, even though the resulting proviruses are almost systematically expressed. Here, we reveal that incoming retroviral preintegration complexes trigger the exportin-mediated cytoplasmic export of the SWI/SNF component INI1 and of the nuclear body constituent PML. We further show that the HIV genome associates with these proteins before nuclear migration. In the presence of arsenic, PML is sequestered in the nucleus, and the efficiency of HIV-mediated transduction is markedly increased. These results unveil a so far unsuspected cellular response that interferes with the early steps of HIV replication.
Turelli
P
P
Department of Genetics and Microbiology, University of Geneva, CH-1211 4, Geneva, Switzerland.
Doucas
V
V
Craig
E
E
Mangeat
B
B
Klages
N
N
Evans
R
R
Kalpana
G
G
Trono
D
D
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006678:HIV / Q000235:genetics / Q000254:growth & development*; D015658:HIV Infections / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018160:Receptors, Cytoplasmic and Nuclear; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D014779:Virus Replication / Q000502:physiology*; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D028884:Karyopherins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018160:Receptors, Cytoplasmic and Nuclear; D000071796:SMARCB1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097606:Exportin 1 Protein; C513266:SMARCB1 protein, human; C070576:PML protein, human