HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway

^*The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099; and ^†Agouron Institute, La Jolla, CA 92037

Communicated by Leslie Orgel, Salk Institute for Biological Studies, San Diego, CA (received for review May 28, 1997)

Abstract

The karyophilic properties of the HIV-1 nucleoprotein complex facilitate infection of nondividing cells such as macrophages and quiescent T lymphocytes, and allow the in vivo delivery of transgenes by HIV-derived retroviral vectors into terminally differentiated cells such as neurons. Although the viral matrix (MA) and Vpr proteins have previously been shown to play important roles in this process, we demonstrate here that integrase, the enzyme responsible for mediating the integration of the viral genome in the host cell chromosome, can suffice to connect the HIV-1 preintegration complex with the cell nuclear import machinery. This novel function of integrase reflects the recognition of an atypical bipartite nuclear localization signal by the importin/karyopherin pathway.

Footnotes

↵ ‡ To whom reprint requests should be addressed. e-mail: trono{at}salk.edu.
ABBREVIATIONS:

NLS,

nuclear localization signal(s);

MA,

matrix;

IN,

integrase;

GST,

glutathione S-transferase;

RT,

reverse transcriptase;

NC,

nucleocapsid;

CA,

capsid