Molecular and phenotypic characteristics of neurotropic HIV-1 subtype E

Abstract

Although HIV-1 subtype E associated with neurological dysfunction is common, the virological characteristics of HIV-1 isolated from the CNS for this subtype have not yet been identified. In this study, paired blood and CSF isolated from patients with AIDs-defining illnesses were cultured, sequenced and aligned. Phylogenetic tree and nucleotide-distances from both blood and CSF were investigated. Cytopathicity and co-receptor usage of paired blood and CSF isolates were compared to define the specific characteristics of CNS isolates. The results confirmed that CSF isolates showed less cytopathicity. It was found that both blood and CSF isolates used either CXCR4 or CXCR4 and CCR5 as co-receptors. Interestingly, one CSF isolate using CCR3 as a co-receptor was identified. By sequence analysis, the pair-wise distances of envelope gp 120 sequence and those of all variable regions (except V3 region) between blood and CSF isolates were significantly different. The genetic distances in V1/V2 regions of CSF isolates showed more diversity than those of blood isolates. These findings suggest that the evolution of V1/V2 regions of CSF isolates seems to be an advantage for HIV-1 in CNS infection. In contrast, the genetic distance in V4 and V5 regions of CSF isolates showed less diversity, suggesting that conservation in these regions might be necessary during the process of HIV-1 CNS infection.