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Journal of Virology, May 2008, p. 5104-5108, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.01897-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mutations in the Human Immunodeficiency Virus Type 1 Polypurine Tract (PPT) Reduce the Rate of PPT Cleavage and Plus-Strand DNA Synthesis{triangledown} ,{dagger}

M. J. McWilliams,1 J. G. Julias,2,{ddagger} and S. H. Hughes1*

HIV Drug Resistance Program, National Cancer Institute at Frederick,1 Basic Research Program, SAIC-Frederick, Inc., Frederick, Maryland 21702-12012

Received 30 August 2007/ Accepted 21 February 2008

Previously, we analyzed the effects of point mutations in the human immunodeficiency virus type 1 (HIV-1) polypurine tract (PPT) and found that some mutations affected both titer and cleavage specificity. We used HIV-1 vectors containing two PPTs and the D116N integrase active-site mutation in a cell-based assay to measure differences in the relative rates of PPT processing and utilization. The relative rates were measured by determining which of the two PPTs in the vector is used to synthesize viral DNA. The results indicate that mutations that have subtle effects on titer and cleavage specificity can have dramatic effects on rates of PPT generation and utilization.

* Corresponding author. Mailing address: HIV Drug Resistance Program, NCI at Frederick, P.O. Box B, Bldg. 539, Rm. 130A, Frederick, MD 21702-1201. Phone: (301) 846-1619. Fax: (301) 846-6966. E-mail: hughes{at}ncifcrf.gov

{triangledown} Published ahead of print on 5 March 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Booz Allen Hamilton, Rockville, MD 20852.

Journal of Virology, May 2008, p. 5104-5108, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.01897-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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