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.

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Cell proliferation is necessary for proviral integration and productive infection of most retroviruses. Nevertheless, the human immunodeficiency virus (HIV) can infect non‐dividing macrophages. This ability to grow in non‐dividing cells is not specific to macrophages because, as we show here, CD4+ HeLa cells arrested at stage G2 of the cell cycle can be infected by HIV‐1. Proliferation is necessary for these same cells to be infected by a murine retrovirus, MuLV. HIV‐1 integrates into the arrested cell DNA and produces viral RNA and protein in a pattern similar to that in normal cells. In addition, our data suggest that the ability to infect non‐dividing cells is due to one of the HIV‐1 core virion proteins. HIV infection of non‐dividing cells distinguishes lentiviruses from other retroviruses and is likely to be important in the natural history of HIV infection.

The human immunodeficiency virus productively infects and integrates into cells that have been arrested in the cell cycle with either gamma irradiation or aphidicolin. Integration by oncoretroviruses such as the murine leukemia virus (MuLV), on the other hand, depends on cell proliferation. Although the entire cell cycle is not necessary for MuLV infection, it is essential that the infected cells pass through mitosis. The long terminal repeat circle junction, a marker for nuclear entry, is first observed in MuLV-infected cells immediately after mitosis. These results suggest that mitosis is necessary for nuclear entry of MuLV, but not human immunodeficiency virus, unintegrated proviral DNA.