A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells.
Permissiveness of the host cell to productive infection by oncoretroviruses is cell-cycle dependent, and nuclear localization of viral nucleoprotein preintegration complexes will occur only after cells have passed through mitosis. In contrast, establishment of an integrated provirus after infection by the lentivirus HIV-1 is independent of host cell proliferation. The ability of HIV-1 to replicate in non-dividing cells is partly accounted for by the karyophilic properties of the viral preintegration complex which, after virus infection, is actively transported to the host cell nucleus. Here we report that the gag matrix protein of HIV-1 contains a nuclear localization sequence which, when conjugated to a heterologous protein, directs its nuclear import. In addition, HIV-1 mutants containing amino-acid substitutions in this nuclear localization signal integrate and replicate within dividing but not growth-arrested cells, and thus display a phenotype more representative of an oncoretrovirus.
Bukrinsky
M I
MI
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5120.
Haggerty
S
S
Dempsey
M P
MP
Sharova
N
N
Adzhubel
A
A
Spitz
L
L
Lewis
P
P
Goldfarb
D
D
Emerman
M
M
Stevenson
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000382:microbiology; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis; D004173:Dipodomys; D016195:G2 Phase; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015683:Gene Products, gag; D015488:HIV Antigens; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D012710:Serum Albumin, Bovine