Modulation by Morphine of Viral Set Point in Rhesus Macaques Infected with Simian Immunodeficiency Virus and Simian-Human Immunodeficiency Virus

Abstract

Six rhesus macaques were adapted to morphine dependence by injecting three doses of morphine (5 mg/kg of body weight) for a total of 20 weeks. These animals along with six control macaques were infected intravenously with mixture of simian-human immunodeficiency virus KU-1B (SHIV KU-1B ), SHIV 89.6P , and simian immunodeficiency virus 17E-Fr. Levels of circulating CD4؉ T cells and viral loads in the plasma and the cerebrospinal fluid were monitored in these macaques for a period of 12 weeks. Both morphine and control groups showed precipitous loss of CD4 ؉ T cells. However this loss was more prominent in the morphine group at week 2 (P ‫؍‬ 0.04). Again both morphine and control groups showed comparable peak plasma viral load at week 2, but the viral set points were higher in the morphine group than that in the control group. Likewise, the extent of virus replication in the cerebral compartment was more pronounced in the morphine group. These results provide a definitive evidence for a positive correlation between morphine and levels of viral replication.

Neuroimmunity and the Blood–Brain Barrier: Molecular Regulation of Leukocyte Transmigration and Viral Entry into the Nervous System with a Focus on NeuroAIDS

“…These findings suggest that morphine may increase both HIV binding to and infection of PBMCs and may be astrocytes (Mahajan et al 2002;Steele et al 2003). Studies of SIV-infected macaques that received morphine demonstrated increased CCR5 expression on PBMCs, as well as increased viral replication in the CNS (Suzuki et al 2002;Kumar et al 2004). …”

HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines

“…Opiate abuse has been shown to increase inflammatory events within the CNS (Anthony et al, 2004;Arango et al, 2004). Recent findings indicate that chronic opiate abuse increases simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV) load in the serum and cerebrospinal fluid (CSF) of nonhuman primates (Kumar et al, 2004) and significantly worsens CD4…”

Analysis of the V1V2 Region of the SIV Envelope in the Brains of Morphine-Dependent and Control SIV/SHIV-Infected Macaques

“…2,3,6,7 In addition, in vitro and in vivo studies have demonstrated a correlation between drugs of abuse and increased viral replication. [8][9][10][11][12][13][14] We have developed a reproducible nonhuman primate model of IDU and HIV disease that utilizes a neuropathogenic SIV (SIV=17E-Fr) and two SHIVs (SHIV KU1-B and SHIV 89.6 P) in Indian rhesus macaques. 13,14 The use of these three viruses leads to massive CD4 þ T cell loss and neurological disorders mimicking comparable clinical manifestations in humans.…”

“…[8][9][10][11][12][13][14] We have developed a reproducible nonhuman primate model of IDU and HIV disease that utilizes a neuropathogenic SIV (SIV=17E-Fr) and two SHIVs (SHIV KU1-B and SHIV 89.6 P) in Indian rhesus macaques. 13,14 The use of these three viruses leads to massive CD4 þ T cell loss and neurological disorders mimicking comparable clinical manifestations in humans. Briefly, morphine dependence was established by injecting increasing doses of morphine (1-5 mg=kg of body weight over a 2-week period) by the intramuscular route at 8-h intervals.…”