期刊
JOURNAL OF VIROLOGY
卷 79, 期 13, 页码 7959-7966出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.13.7959-7966.2005
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资金
- NCI NIH HHS [T32 CA09156, T32 CA009156] Funding Source: Medline
- NIAID NIH HHS [AI54999, P30 AI050410, T32 AI007419, P30 AI054999, AI50410] Funding Source: Medline
- NIMH NIH HHS [R01 MH67751, R01 MH067751] Funding Source: Medline
Human immunodeficiency virus type I (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.
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