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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Early physiological abnormalities after simian immunodeficiency virus infection
T F Horn1, S Huitron-Resendiz, M R Weed
1Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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.
Insights
Early simian immunodeficiency virus (SIV) infection in monkeys causes physiological changes, including disrupted circadian rhythms and reduced motor activity. These abnormalities may signal future central nervous system (CNS) dysfunction.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Central nervous system (CNS) damage is a severe outcome of HIV infection.
- Early viral-induced abnormalities affecting CNS function remain poorly understood.
Purpose of the Study:
- To detect and characterize early physiological abnormalities in simian immunodeficiency virus (SIV)-infected monkeys.
- To identify potential biomarkers for early CNS dysfunction.
Main Methods:
- Monitoring physiological parameters (body temperature, motor activity) in SIV-infected monkeys postinoculation.
- Analyzing sensory-evoked responses, specifically auditory-evoked potentials.
Main Results:
- Acute SIV infection disrupted circadian rhythms, causing hyperthermia and reduced motor activity (50% of control levels) within 1-2 weeks.
- Hyperthermia persisted for 2 months, while motor activity initially recovered then declined again.
- Auditory-evoked potential latencies showed distinct, persistent changes at 1 and 3 months postinoculation.
Conclusions:
- Early physiological abnormalities, including circadian disruption and altered sensory responses, occur during SIV infection.
- These findings suggest potential preclinical indicators of CNS dysfunction.
- The observed abnormalities may serve as an assay for evaluating therapeutic agents targeting neuronal dysfunction.
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