Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques

Rakesh Kumar, Suheydi Orsoni, Lisa Norman, Ashish S. Verma, Grissell Tirado, Luis D. Giavedoni, Silvija Staprans, Gregory M. Miller, Shilpa J. Buch, Anil Kumar

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58 Scopus citations

Abstract

Six morphine-exposed and 3 control male Indian rhesus macaques were intravenously inoculated with mixture of SHIVKU, SHIV89.6P and SIV/17E-Fr. These animals were followed for a period of 56 weeks in order to determine CD4 and CD8 profile, viral loads in plasma and cerebrospinal fluid (CSF), relative distribution of 3 pathogenic viruses in blood and brain, binding as well neutralizing antibody levels and cellular immune responses. Both morphine-exposed and control macaques showed a precipitous loss of CD4+ T cells; control animals, however, showed a greater tendency to recover these cells than did their morphine-exposed counterparts. The plasma and CSF viral loads were significantly higher in morphine-exposed group than those in the control group. Four morphine-exposed animals succumbed to SIV/SHIV-induced AIDS at week 18, 19, 20 and 51; post-infection with neurological disorders was found in 3 of the 4 animals. At the end of the 56-week observation period, 2 morphine-exposed and 3 control animals were still alive. All 3 viruses replicated in the blood of both morphine-exposed and control macaques, but the cerebral compartment showed a selection phenomenon; only SIV/17E-Fr and SHIVKU successfully crossed the blood brain barrier (BBB). The morphine-exposed macaques further favored viral migration through the blood brain barrier (BBB). SIV/17E-Fr crossed the BBB within 2 weeks in both morphine-exposed and control macaques, whereas SHIVKU crossed the BBB more rapidly in morphine-exposed than in control macaques. Three morphine-exposed macaques (euthanized at weeks 18, 19 and 20) did not develop cellular or humoral immune responses, whereas the other 3 morphine-exposed and 3 control macaques developed both cellular and humoral immune responses.

Original languageEnglish (US)
Pages (from-to)192-206
Number of pages15
JournalVirology
Volume354
Issue number1
DOIs
StatePublished - Oct 10 2006
Externally publishedYes

Keywords

  • AIDS
  • Indian rhesus macaques
  • Morphine
  • SHIV
  • SIV

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Kumar, R., Orsoni, S., Norman, L., Verma, A. S., Tirado, G., Giavedoni, L. D., Staprans, S., Miller, G. M., Buch, S. J., & Kumar, A. (2006). Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques. Virology, 354(1), 192-206. https://doi.org/10.1016/j.virol.2006.06.020