title: An in vitro model of morphine withdrawal manifests the enhancing effect on human immunodeficiency virus infection of human T lymphocytes through the induction of substance P.
abstract: Opioid withdrawal is a crucial and recurring event during the course of opioid abuse that has a negative impact on the immune system. In this study, we investigated whether abrupt withdrawal (AW) or precipitated withdrawal (PW) potentiates human immunodeficiency virus (HIV) infection of human T lymphocytes. AW and PW enhanced HIV infection of peripheral blood lymphocytes and T-cell lines (Jurkat and CEMX174). In addition, both AW and PW induced HIV replication in a latently HIV-infected human T-cell line (J1.1). The enhancing effect of AW and PW was associated with the induction of neuropeptide substance P in both peripheral blood lymphocytes and the T-cell lines. The substance P receptor antagonist, CP-96,345, not only blocked AW- or PW-induced endogenous substance P expression but also abrogated AW- or PW-induced HIV replication in T cells. These findings provide a cellular mechanism that supports the notion that opioids have a co-factor role in promoting HIV infection of the immune cells.
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Peng
authors.forename: Dun-Jin
authors.initials: DJ
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D001713:Biphenyl Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D009020:Morphine / Q000009:adverse effects* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013373:Substance P; D009020:Morphine; C066892:CP 96345