Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes.
All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter cells. Simian immunodeficiency virus (SIV) infection of non-human primates has served as a useful model for understanding AIDS pathogenesis in humans. Research on several genetically divergent SIV isolates has revealed that SIV uses CCR5, and not CXCR4, for entry. CEM x174, a human lymphoid cell line, has been routinely used to cultivate and maintain various SIV strains. However, questions have arisen about how CEM x174, which reportedly was unable to express detectable amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching for an answer, we resorted to a sensitive competitive reverse transcriptase-polymerase chain reaction procedure in an attempt to detect as well as quantify the amount of CCR5 expression. Here we present our findings, which indicate that CEM x174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells pretreated with morphine. These results correlate well with our previous observations that morphine treatment causes CEM x174 cells to be more susceptible to SIV infection. Similar morphine effect was not observed on CEM x174 cells infected with simian retroviruses, which do not depend on CCR5 for entry. These findings suggest a plausible mechanism whereby opiate drug users render themselves more susceptible to HIV infection, thereby explaining the vast prevalence of HIV infection among endemic drug use populations.
Miyagi
T
T
Department of Medical Pharmacology and Toxicology, the Section of Molecular and Cellular Biology, University of California, Davis, California 95616, USA.
Chuang
L F
LF
Doi
R H
RH
Carlos
M P
MP
Torres
J V
JV
Chuang
R Y
RY
D001402:B-Lymphocytes / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D015658:HIV Infections / Q000209:etiology; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000378:metabolism; D011991:Receptors, Virus; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000378:metabolism; D019966:Substance-Related Disorders; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
C106330:CXCR6 protein, human; C103539:GPR15 protein, human; D009292:Narcotic Antagonists; D009294:Narcotics; D019713:Receptors, CCR5; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011991:Receptors, Virus; D009270:Naloxone; D009020:Morphine