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Journal of Virology, December 2000, p. 11811-11824, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Human Nuclear Shuttling Protein That Interacts with Human Immunodeficiency Virus Type 1 Matrix Is Packaged into Virions

Kalpana Gupta,1 David Ott,2 Thomas J. Hope,3 Robert F. Siliciano,1,4 and Jef D. Boeke1,*

Department of Molecular Biology and Genetics1 and Department of Medicine,4 Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; AIDS Vaccine Program, National Cancer Institute- Frederick Cancer Research and Development Center, Frederick, Maryland 217022; and Infectious Disease Laboratory, The Salk Institute, La Jolla, California 920373

Received 14 April 2000/Accepted 25 September 2000

Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55Gag and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4+ T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55Gag and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport.

* Corresponding author. Mailing address: Department of Molecular Biology and Genetics, JHU School of Medicine, Baltimore, MD 21205-2185. Phone: (410) 955-2481. Fax: (410) 614-2987. E-mail: jboeke{at}jhmi.edu.

Journal of Virology, December 2000, p. 11811-11824, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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