A NUCLEAR-LOCALIZATION SIGNAL WITHIN HIV-1 MATRIX PROTEIN THAT GOVERNS INFECTION OF NONDIVIDING CELLS

PERMISSIVENESS of the host cell to productive infection by onco-retrov iruses is cell-cycle dependent1, and nuclear localization of viral nuc leoprotein preintegration complexes will occur only after cells have p assed through mitosis2. In contrast, establishment of an integrated pr ovirus after infection by the lentivirus HIV-1 is independent of host cell proliferation3-5. The ability of HIV-1 to replicate in non-dividi ng cells is partly accounted for by the karvophilic properties of the viral preintegration complex which, after virus infection, is actively transported to the host cell nucleus. Here we report that the gag mat rix protein of HIV-1 contains a nuclear localization sequence which, w hen 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 b ut not growth-arrested cells, and thus display a phenotype more repres entative of an onco-retrovirus.