Methadone induces CCR5 and promotes AIDS virus infection.
Methadone, a regimen for the treatment of opioid dependency, was found to induce the expression of CCR5, a co-receptor for human immunodeficiency virus (HIV)/simian form of HIV (SIV) entry, on human CEM x174 lymphocytes. Both CCR5 mRNA and protein were elevated in methadone-treated cells. A concomitant increase of mu opioid receptors was also observed. Upon methadone exposure, SIVmac239-infected CEM x174 cells released greater amounts of virus particles as revealed by both the number of syncytia formation and reverse transcriptase activities. Similar methadone effect was not observed on CEM x174 cells infected with other simian retroviruses that do not depend on CCR5 for cellular entry. These studies raise concerns considering methadone as an innocuous morphine substitute.
Suzuki
Shunji
S
Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA.
Carlos
Maria P
MP
Chuang
Linda F
LF
Torres
José V
JV
Doi
Roy H
RH
Chuang
Ronald Y
RY
D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D015726:Giant Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D008691:Methadone / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D012192:Retroviridae Infections / Q000378:metabolism / Q000821:virology; D015301:Retroviruses, Simian / Q000254:growth & development; D015302:Simian Immunodeficiency Virus / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects
D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D019713:Receptors, CCR5; D017450:Receptors, Opioid, mu; D009270:Naloxone; D012194:RNA-Directed DNA Polymerase; D008691:Methadone