HIV-1 env diversity during primary infection and in the presence of neurological disease

Human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus of the Retroviridae family of viruses. The HIV-1 genome is highly variable, and genetically distinct viral variants co-exist within individuals with established infection. The majority of diversity is localized to the variable domains of the envelope (env) gene. A reduction in viral diversity occurs during HIV-1 transmission. Heteroduplex tracking assays (HTA) specific to the env variable domains were used to assess the complexity of the virus population following transmission. A role for cells containing multiple HIV-1 proviruses is suggested by the frequent transmission of multiple variants despite relatively low transmission rates. Viral diversity following transmission was found to be dependent on the mode of transmission, with men infected through homosexual contact and women infected through heterosexual contact displaying multiple variants in greater than 50% of subjects. Conversely, men infected through heterosexual contact were infected with a homogeneous viral population. Transmitted virus showed no evidence for selection of variants with shorter env sequences. CCR5 co-receptor-using variants predominated while transmission of CXCR4-using variants was rare (3%), but consistently detected in two independent primary infection cohorts. The compartmentalization of viral variants between the cerebral spinal fluid (CSF) and periphery was not evident during primary infection. Compartmentalization of HIV-1 variants later in infection is thought to contribute to the development of HIV-1-associated dementia (HAD). We found that in subjects with HAD a greater percentage of the viral load in the CSF originated from central nervous system (CNS)-specific sources. This suggests that during HAD there is a higher level of replication of CNS-specific variants as reflected in the virus that accumulates in the CSF.