Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem.

OBJECTIVES: HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. MATERIALS AND METHODS: Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). RESULTS: Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. CONCLUSIONS: We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.

Effects of prenatal alcohol exposure on activity and learning in Sprague-Dawley rats.

Nulliparous pregnant Sprague-Dawley rats were exposed to ethanol via a liquid diet technique (FAE, fetal alcohol exposure) or administered a fixed amount of control diet from gestational day 11 to day 21. The offspring, at 2-3 months of age, were studied in tests of mechanically monitored motor activity and learning acquisition in an automatized testing cage requiring an instrumental discriminative response, where the ability to learn and relearn correlations of a light signal to water presentation was monitored. A significantly reduced activity (i.e. ramp mounting behaviour) in a novel situation was obtained in the FAE group compared to controls. The initial disruption of ramp mounting behaviour could reflect alterations in either habituation to a novel test situation, altered neophobia, or some retardation in associating these responses with the outcome of water-availability. Adult FAE rats (six months of age) showed a tendency towards a lowered acquisition performance (p = 0.06) when tested in a circular Morris-type swim maze, but no detectable differences were shown in a motor activity test chamber situation.