AEGiS-05CROI: HIV-1 Vpr enters the nucleus via a novel import pathway.

5th Conference on Retroviruses and Opportunistic Infections

Chicago, IL - February 1-5, 1998

HIV-1 Vpr enters the nucleus via a novel import pathway.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:84 (abstract no. 26)

Jenkins Y, McIntee M, Kuo A, Weis K, Greene WC; Gladstone Institute of Virology and Immunology, San Francisco, CA.

The HIV accessory protein, Vpr, is a small virion-associated protein that is required for viral infection of non-dividing macrophages and induces G2 cell cycle arrest in proliferating cells. Both of these functions appear to depend upon the nuclear import of Vpr. The mechanism by which Vpr traverses the nuclear envelope is not well-understood. By following the localization of a Vpr-beta-galactosidase fusion protein both in vivo and in vitro, we have been able to compare the import pathway for Vpr to the established pathways for proteins containing a classical positively charged nuclear localization signal (NLS) (importin alpha/importin beta dependent) and for hnRNP A1 (transportin dependent). We have found that Vpr utilizes an import pathway with similar energy requirements (Ran/TC4 dependent) but distinct receptor requirements (importin alpha, importin beta, and transportin independent). Mutagenesis studies of Vpr have further revealed the presence of two discrete nuclear localization signals. Together, our data indicate that Vpr uses a novel active import pathway(s) to promote nuclear uptake of the HIV preintegration complex. Further understanding this fundamental process may provide new opportunities to interfere with this critical step in the HIV life cycle.

Keywords: AEGIS, Cell Nucleus, Gene Products, vpr, Heterogeneous-Nuclear Ribonucleoproteins, Nuclear Localization Signal, Nuclear Envelope, HIV-1, Ribonucleoproteins, Karyopherins, Active Transport, Cell Nucleus, Macrophages, alpha Karyopherins, Carrier Proteins, In Vitro, genetics, AIDS

1998-02-01
26

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.