Two HIV Variants Identified in HIV-Linked Dementia
CCR5 T cell-tropic, macrophage-tropic HIV-1 virus present in CSF of patients with HIV dementia
FRIDAY, Oct. 7 (HealthDay News) -- Individuals with HIV-type 1 (HIV-1)-associated dementia (HAD) have two genetically distinct HIV-1 variants in their cerebrospinal fluid (CSF): CCR5-tropic (R5) T-cell-tropic and macrophage-tropic, which differ in terms of replication and evolution in the central nervous system (CNS), according to a study published online Oct. 6 in PLoS Pathogens.
Gretja Schnell, from the University of North Carolina at Chapel Hill, and colleagues investigated the virological characteristics of HIV-1 in the CSF of patients with HAD to examine the correlation between independent viral replication in the CNS and dementia development.
The investigators identified genetically-compartmentalized R5 T-cell-tropic and macrophage-tropic HIV-1 populations in the CSF of patients with HAD. The macrophage-tropic HIV-1 virus population showed genetic divergence, could enter cells with low levels of surface CD4, and their presence was associated with slow viral decay in the CSF. In contrast, the R5 T-cell-tropic HIV-1 virus population was clonally amplified, associated with pleocytosis, required high levels of surface CD4 to enter cells, and was associated with rapid decay of virus in the CSF on initiation of therapy. Macrophage-tropic viruses were mainly restricted to the CNS/CSF compartment rather than the blood.
"These results suggest that HIV-1 variants in CSF can provide information about viral replication and evolution in the CNS, events that are likely to play an important role in HIV-associated neurocognitive disorders," the authors write.