A correlation between HIV-1 infection and intravenous opioid abuse has been established, but the drugs' role in HIV-1 induced disease progression is still uncertain. In addition, alkaloid opiates and endogenous opioid peptides have been shown to alter immune function. Therefore, since opioids can modulate immune activity, there is considerable need to understand the role of opioids in the progress of HIV replication. The current practice of administering opioids as analgesics for treatment of pain in HIV-1 infected individuals and the high risk of HIV infection associated with intravenous drug use suggest the importance of investigating the potential interaction between opioids with HIV-1 infected cells. This proposal seeks to identify the mechanism by which opioids modulate HIV-1 replication and expression, and whether opioids act by modulating the expression of chemokines and their receptors. The proposal will be adressed by the following series of experiements. First, the effects of several selective opioids on the expression of both M-tropic and T-tropic strains of HIV-1 will be examined by reverse trancriptase assay, P24 ELISA, and syncytia counts. Second, T cell lines will be engineered to express opioid receptors to further examine the role of opioid receptors on HIV replication. Lastly, the effects of opioids on the expression of the critical chemokines and chemokine receptors during HIV-1 infection will be measured by RNase protection assay.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA005894-01
Application #
2710711
Study Section
Special Emphasis Panel (ZDA1-MXS-M (01))
Project Start
1999-02-27
Project End
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Temple University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Happel, Christine; Kutzler, Michele; Rogers, Thomas J (2011) Opioid-induced chemokine expression requires NF-?B activity: the role of PKC?. J Leukoc Biol 89:301-9
Happel, Christine; Steele, Amber D; Finley, Matthew J et al. (2008) DAMGO-induced expression of chemokines and chemokine receptors: the role of TGF-beta1. J Leukoc Biol 83:956-63
Szabo, Imre; Wetzel, Michele A; Zhang, Ning et al. (2003) Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization. J Leukoc Biol 74:1074-82
Szabo, Imre; Manning, Michael R; Radzievsky, Alexander A et al. (2003) Low power millimeter wave irradiation exerts no harmful effect on human keratinocytes in vitro. Bioelectromagnetics 24:165-73
Wetzel, Michele A; Steele, Amber D; Henderson, Earl E et al. (2002) The effect of X4 and R5 HIV-1 on C, C-C, and C-X-C chemokines during the early stages of infection in human PBMCs. Virology 292:6-15
Le, Y; Wetzel, M A; Shen, W et al. (2001) Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors. Clin Immunol 99:365-72
Li, B Q; Wetzel, M A; Mikovits, J A et al. (2001) The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. Blood 97:2941-7
Szabo, I; Wetzel, M; McCarthy, L et al. (2001) Interactions of opioid receptors, chemokines, and chemokine receptors. Adv Exp Med Biol 493:69-74
McCarthy, L; Wetzel, M; Sliker, J K et al. (2001) Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 62:111-23