This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Woodward, C. L.
Right arrow Articles by Chow, S. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woodward, C. L.
Right arrow Articles by Chow, S. A.

 Previous Article  |  Next Article 

Journal of Virology, July 2009, p. 6522-6533, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02061-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Integrase Interacts with Nucleoporin NUP153 To Mediate the Nuclear Import of Human Immunodeficiency Virus Type 1 {triangledown}

Cora L. Woodward,1,2 Sarin Prakobwanakit,1 Sherly Mosessian,1 and Samson A. Chow1,2*

Department of Molecular and Medical Pharmacology,1 UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California 900952

Received 30 September 2008/ Accepted 6 April 2009

The ability to traverse an intact nuclear envelope and productively infect nondividing cells is a salient feature of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses, but the viral factors and mechanism of nuclear entry have not been defined. HIV-1 integrase (IN) is implicated to play a role in the nuclear import of the virus, but the cellular pathway for IN trafficking and the role of IN in mediating the nuclear import of viral particles are unknown. Using a semipermeabilized cell assay, we observed that the nuclear import of IN was not the result of passive diffusion but occurred independently of cytosolic factors, metabolic energy, and the classical receptor-mediated, Ran-dependent import pathways. To determine if IN enters the nucleus by interacting with the nucleopore complex (NPC), we found that IN bound directly with the FxFG-rich C-terminal domain of nucleoporin 153 (NUP153C). When added in excess to the import assay, NUP153C inhibited the nuclear import of IN. Known binding partners of NUP153C competed with IN for binding with NUP153 and also inhibited the nuclear import of IN. In cultured cells, overexpression of NUP153C reduced the infectivity of an HIV-derived vector by interfering with the nuclear translocation of the viral cDNA. These results support a functional role for the IN-NUP153 interaction in HIV-1 replication and suggest that HIV-1 subviral particles gain access to the nucleus by interacting directly with the NPC via the binding of particle-associated IN to NUP153C.

* Corresponding author. Mailing address: UCLA School of Medicine, Los Angeles, CA 90095. Phone: (310) 825-9600. Fax: (310) 825-6267. E-mail: schow{at}mednet.ucla.edu

{triangledown} Published ahead of print on 15 April 2009.

Journal of Virology, July 2009, p. 6522-6533, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02061-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»