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Journal of Virology, June 2007, p. 6146-6150, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00203-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Bearing a Disrupted Central DNA Flap Is Pathogenic In Vivo{triangledown}

Matthew D. Marsden1,3 and Jerome A. Zack1,2,3*

Department of Medicine, Division of Hematology and Oncology,1 Department of Microbiology, Immunology, and Molecular Genetics,2 UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 900953

Received 29 January 2007/ Accepted 18 March 2007

The central DNA flap is an important component of lentiviral vectors, but its significance in the context of wild-type human immunodeficiency virus (HIV) is currently unclear. To address this issue, we have compared the in vitro infection kinetics of NL4-3 with those of a flap-deficient mutant and evaluated the in vivo growth characteristics of these viruses by using the SCID-hu mouse model of HIV infection. Flap-deficient virus was only modestly attenuated in vitro, as assessed by single-round and spreading infection assays, and exhibited levels of replication and pathogenesis close to those of the wild-type in vivo. Hence, an intact central flap is not essential for HIV replication.

* Corresponding author. Mailing address: David Geffen School of Medicine at UCLA, 650 Charles Young South, Box 951678, 11-934 Factor, Los Angeles, CA 90095-1678. Phone: (310) 825-0876. Fax: (310) 825-6192. E-mail: jzack{at}ucla.edu

{triangledown} Published ahead of print on 28 March 2007.

Journal of Virology, June 2007, p. 6146-6150, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00203-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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