Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication

Virology. 2003 Apr 25;309(1):99-107. doi: 10.1016/s0042-6822(03)00015-1.


A substantial proportion of HIV-1-infected individuals are intravenous drug users (i.v.DUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the mu-opioid receptor. Our results show that DAMGO, a selective mu-opioid agonist, increases CXCR4 and CCR5 expression in both CD3(+) lymphoblasts and CD14(+) monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the mu-opioid receptor based on the ability of a mu-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of mu-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA Primers
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • HIV Core Protein p24 / genetics
  • HIV Long Terminal Repeat
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Humans
  • Polymerase Chain Reaction
  • Receptors, CCR5 / genetics*
  • Receptors, CXCR4 / genetics*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / physiology*
  • Virus Replication / drug effects
  • Virus Replication / physiology*


  • DNA Primers
  • HIV Core Protein p24
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-