Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus–infected monkeys
Howard S. Fox, … , Norbert Bischofberger, Steven J. Henriksen
Howard S. Fox, … , Norbert Bischofberger, Steven J. Henriksen
Published January 1, 2000
Citation Information: J Clin Invest. 2000;106(1):37-45. https://doi.org/10.1172/JCI9102.
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Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus–infected monkeys

Abstract

Simian immunodeficiency virus (SIV) infection of rhesus monkeys provides an excellent model of the central nervous system (CNS) consequences of HIV infection. To discern the relationship between viral load and abnormalities induced in the CNS by the virus, we infected animals with SIV and later instituted antiviral treatment to lower peripheral viral load. Measurement of sensory-evoked potentials, assessing CNS neuronal circuitry, revealed delayed latencies after infection that could be reversed by lowering viral load. Cessation of treatment led to the reappearance of these abnormalities. In contrast, the decline in general motor activity induced by SIV infection was unaffected by antiviral treatment. An acute increase in the level of the chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak of acute viremia, likely contributing to an early influx of immune cells into the CNS. Examination of the brains of the infected animals after return of the electrophysiological abnormalities revealed diverse viral and inflammatory findings. Although some of the physiological abnormalities resulting from SIV infection can be at least temporarily reversed by lowering viral load, the viral-host interactions initiated by infection may result in long-lasting changes in CNS-mediated functions.

Authors

Howard S. Fox, Michael R. Weed, Salvador Huitron-Resendiz, Jamal Baig, Thomas F.W. Horn, Peter J. Dailey, Norbert Bischofberger, Steven J. Henriksen

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Figure 2

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Effects of PMPA and SIV infection on movement and temperature. (a) Gross...
Effects of PMPA and SIV infection on movement and temperature. (a) Gross motor activity. Gross motor activity was normalized for each animal to its baseline, and data for each group were expressed as a percentage of baseline along the y-axis. The heights of the boxes indicate the group mean, and the error bars the SEM. Three time periods are delineated: saline injection before PMPA treatment (Saline 1); during PMPA treatment (PMPA); and saline injection after PMPA treatment (Saline 2). In the left panel, data from the SIV-infected (filled boxes) and uninfected (open boxes) animals in this study are shown. A decrease in gross motor activity followed SIV infection regardless of PMPA administration. In the right panel, data are included for comparison from the same period after viral inoculation (indicated in italics) in a previously studied untreated SIV-infected group (10). AThe point differed from baseline condition. BThe groups differed during this condition. (b) Fine motor coordination in the bimanual motor task. The latency to retrieve all 15 raisins is indicated on the y-axis (error bars represent the SEM) for the time points indicated as in a. Despite large changes in gross motor activity, there were no effects of either PMPA or SIV infection on fine motor control in the bimanual motor task. (c) Body temperature. Change in temperature (ΔT) from baseline, plotted on the y-axis with error bars indicating the SEM, was determined by subtracting the baseline mean from each daily mean temperature. The periods analyzed and the animal groups are as in a. An increase in body temperature followed SIV infection regardless of PMPA administration. In the uninfected animals, the injections resulted in a slight increase in body temperature, which was significantly above baseline during the PMPA treatment (left panel). AThe point differs from the baseline condition.