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

Abstract：

: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.

journal_name

Virology

journal_title

Virology

authors

Steele AD,Henderson EE,Rogers TJ

doi

10.1016/s0042-6822(03)00015-1

subject

Has Abstract

pub_date

2003-04-25 00:00:00

pages

99-107

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042682203000151

journal_volume

309

pub_type

杂志文章

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