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Journal of Virology, December 2002, p. 12087-12096, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12087-12096.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Reassessment of the Roles of Integrase and the Central DNA Flap in Human Immunodeficiency Virus Type 1 Nuclear Import

Department of Microbiology,¹ Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148,² The Wistar Institute, Philadelphia, Pennsylvania 19104-4268,³ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024,⁴ Department of Infectious Diseases, Guy's, King's and St. Thomas' School of Medicine, King's College London, London SE1 9RT, United Kingdom⁵

Received 24 May 2002/ Accepted 29 August 2002

Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells productively because the nuclear import of viral nucleic acids occurs in the absence of cell division. A number of viral factors that are present in HIV-1 preintegration complexes (PICs) have been assigned functions in nuclear import, including an essential valine at position 165 in integrase (IN-V165) and the central polypurine tract (cPPT). In this article, we report a comparison of the replication and infection characteristics of viruses with disruptions in the cPPT and IN-V165. We found that viruses with cPPT mutations still replicated productively in both dividing and nondividing cells, while viruses with a mutation at IN-V165 did not. Direct observation of the subcellular localization of HIV-1 cDNAs by fluorescence in situ hybridization revealed that cDNAs synthesized by both mutant viruses were readily detected in the nucleus. Thus, neither the cPPT nor the valine residue at position 165 of integrase is essential for the nuclear import of HIV-1 PICs.

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