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Journal of Virology, August 2009, p. 8254-8258, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00580-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Suppression of Human Immunodeficiency Virus Type 1 (HIV-1) Viremia with Reverse Transcriptase and Integrase Inhibitors, CD4+ T-Cell Recovery, and Viral Rebound upon Interruption of Therapy in a New Model for HIV Treatment in the Humanized Rag2–/–{gamma}c–/– Mouse{triangledown} ,{dagger}

Shailesh K. Choudhary,1* Naser L. Rezk,2 William L. Ince,3 Manzoor Cheema,1 Liguo Zhang,4 Lishan Su,3,4 Ronald Swanstrom,3 Angela D. M. Kashuba,2 and David M. Margolis1,4,5*

Department of Medicine,1 School of Pharmacy,2 Curriculum in Genetics and Molecular Biology,3 Departments of Microbiology and Immunology,4 Epidemiology, University of North Carolina, Chapel Hill, North Carolina 275995

Received 20 March 2009/ Accepted 23 May 2009

A small animal model that reproduces human immunodeficiency virus type 1 (HIV-1) pathogenesis may allow modeling of new therapeutic strategies in ways not approachable in mononuclear cell culture. We find that, as in humans, combination antiretroviral therapy (ART) in humanized (hu-) Rag2–/–{gamma}c–/– mice allows suppression of viremia below the limits of detection and recovery of CD4+ cells, while interruption of ART results in viral rebound and renewed loss of CD4+ T cells. Failure of ART in infected mice is associated with the appearance of drug resistance mutations. The hu-Rag2–/–{gamma}c–/– mouse may therefore facilitate testing of novel approaches to HIV replication and persistence.

* Corresponding authors. Mailing address for S. K Choudhary: University of North Carolina at Chapel Hill, 3206 Michael Hooker Research Ctr., CB#7435, Chapel Hill, NC 27599-7435. Phone: (919) 966-6389. Fax: (919) 966-0584. E-mail: schoudha{at}med.unc.edu. Mailing address for D. M. Margolis: University of North Carolina at Chapel Hill, 3302 Michael Hooker Research Ctr., CB#7435, Chapel Hill, NC 27599-7435. Phone: (919) 966-6388. Fax: (919) 966-0584. E-mail: dmargo{at}med.unc.edu

{triangledown} Published ahead of print on 3 June 2009.

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

Journal of Virology, August 2009, p. 8254-8258, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00580-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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