Ex Vivo Effect of Methadone Use and Withdrawal on Immune Function and HIV-1 Replication of CD4+ T-Cells from Chronic Methadone Patients Drug abuse remains one of the major risk factors for the spread of HIV-1 infection with opiates being a principal drug of concern. Opiates have been shown to be determining factors in the rate of progression of AIDS. The sum of various in vitro, animal-model, and epidemiological studies Indicates that opiates have conditionally variable effects on HIV-1 disease progression. Immunovirological and pharmacological variability are two major factors that seem to dictate whether HIV-1 infection will progress more rapidly or more slowly in HIV-1 infected opiate-exposed individuals. According to previous studies, the immunovirological effect of an opiate drug such as methadone Is not well characterized in an ex vivo human system. The hypothesis to be tested in this proposal is that ex vivo methadone use and withdrawal will enhance HIV-1 infectivity in CD4+ T-lymphocytes by altering cytokine/chemokine profile and upregulating HIV-1 co-receptor and mu-opioid receptor expression.
The specific aims will analyze various immunovirological determinants of HIV-1 infectivity to evaluate the effects of methadone use and withdrawal. CD4+ T-lymphocytes will be obtained from HIV-1 negative healthy volunteers and chronic (more than one year) methadone patients. Cells will be acutely infected with HIV-1 SF2 (X4/R5 dual virus strain) and then assayed to determine how ex vivo methadone exposure (10-7 and 10-6 M) and abrupt withdrawal: (1) affects HIV-1 infectivity (using HIV-1 p24 ELISA);(2) disrupt cytokine/chemokine profile (using cytometric bead array and ELISA);and (3) modulates the gene and protein expression of extracellular and intracellular molecules (using flow cytometry, quantitative RT-PCR, and Western blot). Statistical analysis will be used to determine significant differences between the different experimental conditions. This study will reveal new cellular and molecular mechanisms involved in methadone-mediated HIV-1 replication enhancement. This data can be used to design future in vivo longitudinal studies on the immune and viral modulating effects of methadone in HIV-1 infected methadone patients
This proposed pilot project will attempt to provide well-controlled laboratory data that may lead to new mechanistic understanding of the effect of opiates such as methadone on Immune function and HIV-1 infectivity and provide the basis to develop more effective treatment interventions for the increasing population of HIV-1 infected methadone users.
|Buchacz, Kate; Lau, Bryan; Jing, Yuezhou et al. (2016) Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010. J Infect Dis 214:862-72|
|Fred-JimÃ©nez, Ruth M; Arroyo-Ãvila, MariangelÃ; Mayor, Ãngel M et al. (2016) Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome. J Obes 2016:1379289|
|MÃ©ndez-GonzÃ¡lez, Miguel P; Kucheryavykh, Yuriy V; Zayas-Santiago, Astrid et al. (2016) Novel KCNJ10 Gene Variations Compromise Function of Inwardly Rectifying Potassium Channel 4.1. J Biol Chem 291:7716-26|
|Santiago-RodrÃguez, Eduardo J; Mayor, Angel M; FernÃ¡ndez-Santos, Diana M et al. (2016) Profile of HIV-Infected Hispanics with Pancytopenia. Int J Environ Res Public Health 13:ijerph13010038|
|Inyushin, M; Kucheryavih, Yu; Kucheryavih, L et al. (2016) Superparamagnetic Properties of Hemozoin. Sci Rep 6:26212|
|Morales-Cruz, Moraima; Cruz-MontaÃ±ez, Alejandra; Figueroa, Cindy M et al. (2016) Combining Stimulus-Triggered Release and Active Targeting Strategies Improves Cytotoxicity of Cytochrome c Nanoparticles in Tumor Cells. Mol Pharm 13:2844-54|
|Rivera Rivera, Amilcar; Castillo-Pichardo, Linette; Gerena, Yamil et al. (2016) Anti-Breast Cancer Potential of Quercetin via the Akt/AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Cascade. PLoS One 11:e0157251|
|Althoff, Keri N; Rebeiro, Peter F; Hanna, David B et al. (2016) A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts. J Int AIDS Soc 19:20707|
|Miranda-Diaz, Christine; Betancourt, Elba; Ruiz-Candelaria, Yelitza et al. (2016) Barriers for Compliance to Breast, Colorectal, and Cervical Screening Cancer Tests among Hispanic Patients. Int J Environ Res Public Health 13:ijerph13010021|
|Zueva, Lidia; Golubeva, Tatiana; Korneeva, Elena et al. (2016) Foveolar MÃ¼ller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency. Microsc Microanal 22:379-86|
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