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Journal of Virology, July 2005, p. 7959-7966, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.7959-7966.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Compartmentalized Human Immunodeficiency Virus Type 1 Present in Cerebrospinal Fluid Is Produced by Short-Lived Cells

Patrick R. Harrington,1 David W. Haas,2,3 Kimberly Ritola,5,6 and Ronald Swanstrom1,4,5*

Lineberger Comprehensive Cancer Center,1 Department of Biochemistry and Biophysics,4 UNC Center for AIDS Research,5 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina 27599-7295,6 Departments of Medicine, Microbiology and Immunology,2 Vanderbilt Meharry Center for AIDS Research, Vanderbilt University School of Medicine, Nashville, Tennessee 372033

Received 22 December 2004/ Accepted 29 March 2005

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) during primary infection and persists in this compartment by unknown mechanisms over the course of infection. In this study, we examined viral population dynamics in four asymptomatic subjects commencing antiretroviral therapy to characterize cellular sources of HIV-1 in the CNS. The inability to monitor viruses directly in the brain poses a major challenge in studying HIV-1 dynamics in the CNS. Studies of HIV-1 in cerebrospinal fluid (CSF) provide a useful surrogate for the sampling of virus in the CNS, but they are complicated by the fact that infected cells in local CNS tissues and in the periphery contribute to the population pool of HIV-1 in CSF. We utilized heteroduplex tracking assays to differentiate CSF HIV-1 variants that were shared with peripheral blood plasma from those that were compartmentalized in CSF and therefore presumably derived from local CNS tissues. We then tracked the relative decline of individual viral variants during the initial days of antiretroviral therapy. We found that HIV-1 variants compartmentalized in CSF declined rapidly during therapy, with maximum half-lives of approximately 1 to 3 days. These kinetics emulate the decline in HIV-1 produced from short-lived CD4+ T cells in the periphery, suggesting that a similarly short-lived, HIV-infected cell population exists within the CNS. We propose that short-lived CD4+ T cells trafficking between the CNS and the periphery play an important role in amplifying and maintaining HIV-1 populations in the CNS during the asymptomatic phase of infection.

* Corresponding author. Mailing address: CB#7295, Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-5710. Fax: (919) 966-8212. E-mail: risunc{at}med.unc.edu.

Journal of Virology, July 2005, p. 7959-7966, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.7959-7966.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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