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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Article

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 1

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Effects of PMPA on SIV-induced evoked potential abnormalities. Top: BSAE...
Effects of PMPA on SIV-induced evoked potential abnormalities. Top: BSAEP P5 latencies in groups of four SIV-infected and three uninfected control monkeys. The latency is indicated on the y-axis. SIV-infected animals are indicated by squares, control uninfected animals by circles. Black symbols are the group averages with error bars denoting SEM; colored symbols show data points for the individual animals. After infection, the evoked potential latency is significantly delayed 1–2 months after infection but becomes indistinguishable from preinoculation values after 1 month of PMPA treatment. When treatment is withdrawn, BSAEP latency values remain normal for approximately 2 months, then again become significantly delayed. AThe point differs from baseline. Bottom: Copy equivalents of SIV RNA in the plasma of the infected monkeys. Plasma viral load, indicated on the y-axis (log10 transformed, error bars indicate SEM), peaks at 14 days after inoculation, then reaches a steady-state level. Upon institution of PMPA therapy, viral load drops more than 100-fold but recovers to pretreatment levels upon cessation of therapy.