Viral Evolution in Tissues
April 2, 2003

Tissue sanctuaries, such as the brain, that harbor HIV-1 may require special therapeutic intervention. In a close collaboration with Dr. Richard Price (UCSF), Jutta Neuenburg and others in the laboratory have analyzed specimens from cerebrospinal fluid (CSF) and blood plasma to determine if there was evidence of independent viral replication and evolution in CSF-associated tissues. Phylogenetic analysis of HIV envelope sequences in CSF and plasma samples obtained during therapy from subjects with different levels of CSF pleocytosis and at different stages of AIDS dementia complex (ADC) provided evidence of viral compartmentalization in CSF-associated tissues of subjects with ADC but not in cognitively normal subjects. Dr. Neuenburg directly confirmed that some cells in the CSF produce HIV-1 using a flow cytometry assay to assess production of HIV-1 gag p24 in cells. The number of cells that produce HIV-1 in the CSF appears to decrease in most persons after starting antiretroviral therapy. These studies of CSF viral dynamics and compartmentalization will evaluate the clinical significance of one possible tissue sanctuary for HIV-1 and may help guide the selection of antiretroviral therapy.

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