Independent evolution of HIV type 1 in different brain regions

HIV-1-associated brain pathology exhibits regional variability and we there fore studied the genetic differences in the V1-V5 domains of the HIV env ge ne in up to four regions of brain (frontal lobe, basal ganglia, medial temp oral lobe, and nonmedial temporal lobe) from three patients. We found that in each separate brain region HIV-1 forms different quasispecies and that t here is little gene flow among these regions, In further support of brain r egion-specific evolution of HIV-1, we analyzed amino acid signatures in the se clones. In addition to known amino acid signatures associated with macro phage tropism and the lack of syncytium formation, we found 15 majority ami no acid signature patterns from the V1-V5 env sequences associated with the neuroanatomical regions analyzed from the three individuals. Furthermore, on average, intrabrain genetic distances for the HIV-1 env were estimated t o be much smaller than genetic distances between brain regions. Specific st rains of HIV-1 may be neurotropic or neuroinvasive (replication preference in brain tissue) and may contribute to pathology, cognitive loss, and neuro psychiatric disease.