Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques.
Six morphine-exposed and 3 control male Indian rhesus macaques were intravenously inoculated with mixture of SHIV(KU), SHIV(89.6)P 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 SHIV(KU) 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 SHIV(KU) 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.
Kumar
Rakesh
R
Laboratory of Viral Immunology, AIDS Research Program and Department of Microbiology, Ponce School of Medicine, Ponce, PR 00732, Puerto Rico.
Orsoni
Suheydi
S
Norman
Lisa
L
Verma
Ashish S
AS
Tirado
Grissell
G
Giavedoni
Luis D
LD
Staprans
Silvija
S
Miller
Gregory M
GM
Buch
Shilpa J
SJ
Kumar
Anil
A
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D000818:Animals; D000914:Antibodies, Viral; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002555:Cerebrospinal Fluid / Q000821:virology; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013687:Telencephalon / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D000914:Antibodies, Viral; D012367:RNA, Viral; D009020:Morphine