12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 12

Patrick R Harrington¹, D Haas², and R Swanstrom^3
1Lineberger Cancer Ctr, Univ of North Carolina at Chapel Hill, USA; ²Vanderbilt Meharry Ctr for AIDS Res, Vanderbilt Univ Med Sch, Nashville, TN, USA; and ³Lineberger Cancer Ctr, Univ of North Carolina at Chapel Hill, USA

BACKGROUND: Little is known about the mechanisms by which HIV-1 persists in the central nervous system over the course of infection. We examined HIV-1 population dynamics in asymptomatic subjects to characterize infected cell sources of HIV-1 in the central nervous system. A major challenge in studying HIV-1 dynamics in the central nervous system is the inability to directly monitor viruses in the brain of infected patients. Studies of HIV-1 in cerebrospinal fluid (CSF) provide a useful surrogate for the sampling of virus in the CNS, but are complicated by the fact that infected cells in local central nervous system tissues and in the periphery contribute to the population pool of HIV-1 in CSF.

METHODS: We examined viral population dynamics in CSF and peripheral blood plasma during the initial days of antiretroviral therapy in 4 asymptomatic individuals. Heteroduplex tracking assays targeting the V1/V2 and V4/V5 hypervariable regions of env were used to first distinguish between CSF HIV-1 variants that were either shared with peripheral blood plasma or compartmentalized to CSF, and therefore presumably derived from local central nervous system tissues. Individual CSF HIV-1 variants were then tracked longitudinally by heteroduplex tracking assay and phosphor-imaging to monitor their relative decline during therapy.

RESULTS: Compartmentalized HIV-1 variants in CSF were readily detected by heteroduplex tracking assay. HIV-1 variants compartmentalized in CSF declined rapidly during the initial days of therapy, often more rapidly than CSF variants shared with the peripheral blood. The maximum half-life of compartmentalized HIV-1 variants in CSF were 1 to 3 days, emulating the kinetics of HIV-1 produced by short-lived CD4+ T cells in the periphery.

CONCLUSIONS: These results suggest that a short-lived infected cell population exists within the central nervous system and contributes to the vast majority of compartmentalized HIV-1 in CSF of asymptomatic patients. We propose a model whereby short-lived, uninfected CD4+ T cells trafficking into the central nervous system amplify the HIV-1 population produced by longer-lived cells in the central nervous system. These findings illustrate the dynamic nature of HIV-1 replication in the central nervous system and raise the possibility that trafficking CD4+ T cells play a role in HIV-1 persistence and pathogenesis in the central nervous system.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.