Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex.

Heat-shock proteins (Hsp's) are a family of molecular chaperones that contribute to protection from environmental stress. In this report, we demonstrate that a member of this family, Hsp70, facilitates nuclear import of HIV-1 preintegration complexes (PICs). The mechanism of this activity appears to be similar to the one used by ...
Vpr, an HIV-1 protein regulating viral nuclear import and replication in macrophages. Indeed Hsp70 stimulated binding of HIV-1 matrix antigen to GST-karyopherin alpha fusion protein and rescued nuclear import of a Vpr-defective HIV-1 strain in vitro. Binding studies with truncated forms of GST-karyopherin alpha demonstrated that both Vpr and Hsp70 bind to a region in the amino-terminal part of the karyopherin alpha molecule. This region appears to be distinct from the binding sites for two other karyopherin alpha cargoes, basic-type NLS-containing proteins and transcription factor STAT-1. Vpr competed with Hsp70 for binding to karyopherin alpha. These results suggest the presence of a novel regulatory site on karyopherin alpha which is used by Hsp70 and Vpr to stimulate interaction between the HIV-1 PIC and karyopherin alpha and thus promote viral nuclear import.
Mesh Terms:
Antigens, Polyomavirus Transforming, Binding Sites, Binding, Competitive, Biological Transport, Cell Nucleus, Cytosol, DNA-Binding Proteins, Gene Products, vpr, HIV Infections, HIV-1, HSP70 Heat-Shock Proteins, HeLa Cells, Humans, Kidney, Mutagenesis, Nuclear Proteins, Recombinant Fusion Proteins, STAT1 Transcription Factor, Trans-Activators, Virus Integration, Virus Replication, alpha Karyopherins, vpr Gene Products, Human Immunodeficiency Virus
Exp. Cell Res.
Date: Sep. 15, 2000
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