This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, R. Articles by Engelman, A. Search for Related Content PubMed PubMed Citation Articles by Lu, R. Articles by Engelman, A.

 Previous Article  |  Next Article 

Journal of Virology, October 2005, p. 12584-12591, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12584-12591.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Lys-34, Dispensable for Integrase Catalysis, Is Required for Preintegration Complex Function and Human Immunodeficiency Virus Type 1 Replication

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Received 13 May 2005/ Accepted 5 July 2005

Retroviral integrases (INs) function in the context of preintegration complexes (PICs). Two conserved Lys residues in the N-terminal domain of human immunodeficiency virus type 1 (HIV-1) IN were analyzed here for their roles in integration and virus replication. Whereas HIV-1_K46A grew like the wild type, HIV-1_K34A was dead. Yet recombinant IN_K34A protein functioned in in vitro integration assays, and Vpr-IN_K34A efficiently transcomplemented the infectivity defect of an IN active site mutant virus in cells. HIV-1_K34A was therefore similar to a number of previously characterized mutant viruses that failed to replicate despite encoding catalytically competent IN. To directly analyze mutant PIC function, a sensitive PCR-based integration assay was developed. HIV-1_K34A and related mutants failed to support detectable levels (<1% of wild type) of integration. We therefore concluded that mutations like K34A disrupted higher-order interactions important for PIC function/maturation compared to the innate catalytic activity of IN enzyme.

This article has been cited by other articles:

• Mbisa, J. L., Barr, R., Thomas, J. A., Vandegraaff, N., Dorweiler, I. J., Svarovskaia, E. S., Brown, W. L., Mansky, L. M., Gorelick, R. J., Harris, R. S., Engelman, A., Pathak, V. K. (2007). Human Immunodeficiency Virus Type 1 cDNAs Produced in the Presence of APOBEC3G Exhibit Defects in Plus-Strand DNA Transfer and Integration. J. Virol. 81: 7099-7110 [Abstract] [Full Text]  
• Anderson, J. L., Campbell, E. M., Wu, X., Vandegraaff, N., Engelman, A., Hope, T. J. (2006). Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins. J. Virol. 80: 9754-9760 [Abstract] [Full Text]