Open AccessA nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells
Author(s) -
Michael Bukrinsky,
Sheryl Haggerty,
Michael P. Dempsey,
Н. П. Шарова,
Alexei A. Adzhubei,
L Spitz,
P.F. Lewis,
David S. Goldfarb,
Michael Emerman,
Mario Stevenson
Publication year - 1993
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/365666a0
Subject(s) - nuclear localization sequence , provirus , biology , nuclear transport , viral matrix protein , virology , cell nucleus , permissiveness , retrovirus , nuclear protein , microbiology and biotechnology , heterologous , nls , nucleoprotein , nuclear matrix , virus , viral replication , viral protein , nucleus , genetics , chromatin , dna , genome , gene , transcription factor
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.