66. Differences in HIV-1 V1/V2 and V3 Populations between Blood Plasma and Cerebral Spinal Fluid Suggest at Least Partial Virologic Compartmentalization

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Session 15 Oral Abstract Session
Neuropathogenesis
Session Time: Tuesday, 10 am - 12:30 pm
Room 606-609

11:15 66.

Differences in HIV-1 V1/V2 and V3 Populations between Blood Plasma and Cerebral Spinal Fluid Suggest at Least Partial Virologic Compartmentalization
K. Ritola*, J. A. E. Nelson, K. Robertson, C. Hall, S. A. Fiscus, and R. Swanstrom
Univ. of North Carolina, Chapel Hill

Background: During HIV-1 infection, the gp120 subunit of the viral Env protein is under immune pressure resulting in sequence diversification which allows evasion of the host response. This pressure to evolve results in the appearance of multiple viral variants within a subject. The env gene variable regions 1 and 2 (V1/V2) can be used to reveal this diversification in the form of multiple co-existing genotypes. A cross-sectional analysis of the viral variants present in the blood plasma and cerebral spinal fluid (CSF) from matched timepoints was done to determine which variants were present in each compartment during chronic infection. We also examined the env variable region V3 which encodes a domain that is important in determining co-receptor usage. This region was examined for the genotypic evidence of X4 variants and for further evidence of compartmentalization.
Methods: RNA was extracted from blood plasma and CSF and amplified by RT-PCR. The variability of the V1/V2 and V3 regions of env was then examined using a heteroduplex tracking assay (HTA) with a radiolabeled probe specific for each region. The relative abundance of each viral variant was determined by phospho-imager analysis and the pattern of viral variants was compared between compartments.
Results: For the V1/V2 region, of the 9 subjects examined, 3 (33%) of the subjects had more viral variants present in the CSF than in the blood, 5 (56%) had more variants present in the blood than the CSF, and 1 (11%) had no detectable differences between the compartments. 6 (67%) had differences in the relative abundances of viral variants shared by the two compartments. The V3 region was examined in eight of the 9 patients. 5 (63%) had the same viral variants present in both compartments. 3 (37%) had unique variants in the blood which were not present in the CSF.
Conclusions: There appears to be at least partial compartmentalization of virus between the blood and the CSF resulting in unique variants being present in one or both of the compartments. The appearance of novel species in the CSF suggests that either undetected variants in the blood compartment are selectively enriched in the central nervous system (CNS) compartment, or that a subset of the virus in the CNS can have a separate evolutionary path distinct from the virus in the blood which must undergo multiple rounds of isolated replication.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections