Early physiological abnormalities after simian immunodeficiency virus infection

Abstract

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

“…Subcutaneous body temperature data are not identical to 'core' body temperature but are likely closely correlated in the macaque. For this study, mean temperature before challenge was about 11C lower than values reported for intraperitoneal temperature in Japanese (Takasu et al, 2002) and pigtail (MR Weed, personal communication) macaques; this was consistent with prior reports for subcutaneous temperature in cynomolgous (Almirall et al, 2001) and rhesus (Horn et al, 1998) macaques. The circadian patterns of temperature regulation appear highly similar between s.c. and i.p.…”

Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus–infected monkeys

“…SIV inoculation was performed via the saphenous vein using a cell-free viral stock (SIVmac182) obtained after serial passage of SIVinfected microglia (10). Animals received 1 mL of SIVmac182 in RPMI-1640, containing 0.5 ng/mL p27 (gag) antigen; this dose is equivalent to 10 3 tissue culture infectious doses when titered on CEMx174 cells.…”

“…Continuous movement and temperature analysis was performed using radiotelemetry with implantable transmitters, cage-mounted receivers, and software data acquisition program purchased from Data Sciences (St. Paul, Minnesota, USA) as described previously (10). To account for individual differences in gross motor activity, data from individual monkeys were normalized against the average of a 14-day baseline period (preinoculation for SIV groups, preceding saline injection for the PMPA-only group).…”

“…In situ hybridization was performed as described elsewhere (25) Electrophysiology. Electrophysiological analysis of brainstem auditory-evoked potentials (BSAEPs) was performed on ketamine (20 mg/kg) anesthetized animals as described previously (10,26). Evoked events were analyzed offline using signal averaging capabilities of a microcomputer.…”

High Frequency of Virus-Specific CD8+T Cells in the Central Nervous System of Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251

“…CNS infection occurs during primary SIV infection (7), and the degree of CNS pathology varies among animals (6,17,26,39,48). For chronically infected macaques, a significant decrease in viral RNA is observed in the CNS, even though viral DNA persists (8).…”