Reduced nuclear import of human immunodeficiency virus type 1 preintegration complexes in the presence of a prototypic nuclear targeting signal.
Nuclear import of the retroviral preintegration complex and integration of retroviral with host cell DNA are essential steps for completion of the virus life cycle. The preintegration complex of the lentivirus human immunodeficiency virus type 1 (HIV-1) displays karyophilic properties and, as a consequence, is rapidly directed to the host cell nucleus by an energy-dependent transport pathway. The karyophilic properties of nuclear proteins are governed by a nuclear localization sequence, the targeting function of which can be inhibited in the presence of excess targeting signals. Here we present evidence that the nuclear import of a large karyophile--the preintegration complex of HIV-1--is inhibited in the presence of a prototypic nuclear targeting signal of simian virus 40 T antigen. This points to a novel strategy which prevents establishment of the provirus by interrupting nuclear localization of HIV-1 DNA.
Gulizia
J
J
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5120.
Dempsey
M P
MP
Sharova
N
N
Bukrinsky
M I
MI
Spitz
L
L
Goldfarb
D
D
Stevenson
M
M
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000502:physiology*; D016662:Virus Integration / Q000502:physiology*
D000957:Antigens, Viral, Tumor; D004270:DNA, Circular; D018076:DNA, Complementary; D004279:DNA, Viral; D010446:Peptide Fragments; D021382:Protein Sorting Signals