LOCATION OF THE HIV-1 REV PROTEIN DURING MITOSIS - INACTIVATION OF THE NUCLEAR EXPORT SIGNAL ALTERS THE PATHWAY FOR POSTMITOTIC REENTRY INTO NUCLEOLI

The HIV-1 Rev protein localizes predominantly to the nucleolus of HIV- 1-infected or Rev-expressing cells, The subcellular location of Rev du ring mitotic nucleolar disintegration was examined at various stages o f mitosis in synchronized Rev-expressing CMT3 cells. During early prop hase Rev was predominantly located in disintegrating nucleoli and bega n to accumulate at the peripheral regions of chromosomes in late proph ase, eventually distributing uniformly on all chromosomes in prometaph ase, In anaphase Rev remained associated with the perichromosomal regi ons, but significant amounts of Rev were also seen in numerous nucleol us-derived foci, The movement of Rev from disintegrating nucleoli to p erichromosomal regions and foci was similar to that of nonribosomal nu cleolar proteins, including fibrillarin, nucleolin, protein B23 and p5 2 of the granular component, During telophase Rev remained associated with perichromosomal regions and mitotic foci until the nuclear envelo pe started to reform, When nuclear envelope formation was complete in late telophase, nonribosomal nucleolar proteins were present in prenuc leolar bodies (PNBs) which were eventually incorporated into nucleoli; at the same time, Rev was excluded from nuclei, In contrast, a trans- dominant negative Rev protein containing an inactive nuclear export si gnal reentered nuclei by the nonribosomal nucleolar protein pathway in late telophase, associating with PNBs and reformed nucleoli, Rev prot ein reentry into postmitotic nuclei was delayed until early G(1) phase , but before the arrival of ribosomal protein S6, Thus, Rev behaves li ke a nonribosomal nucleolar protein through mitosis until early teloph ase; however, its nuclear reentry seems to require reestablishment of both a nuclear import system and active nucleoli.