This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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-1SF2 (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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Research Centers in Minority Institutions Award (G12)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Universidad Central Del Caribe
Other Domestic Higher Education
United States
Zip Code
Karl, Anett; Agte, Silke; Zayas-Santiago, Astrid et al. (2018) Retinal adaptation to dim light vision in spectacled caimans (Caiman crocodilus fuscus): Analysis of retinal ultrastructure. Exp Eye Res 173:160-178
Agte, Silke; Savvinov, Alexey; Karl, Anett et al. (2018) Müller glial cells contribute to dim light vision in the spectacled caiman (Caiman crocodilus fuscus): Analysis of retinal light transmission. Exp Eye Res 173:91-108
Suárez-Arroyo, Ivette J; Loperena-Alvarez, Yaliz; Rosario-Acevedo, Raysa et al. (2017) Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer. Medicines (Basel) 4:
Pasaoglu, Taliha; Schikorski, Thomas (2016) Presynaptic size of associational/commissural CA3 synapses is controlled by fibroblast growth factor 22 in adult mice. Hippocampus 26:151-60
Maldonado-Martínez, Gerónimo; Hunter-Mellado, Robert F; Fernández-Santos, Diana et al. (2016) Persistent HIV Viremia: Description of a Cohort of HIV Infected Individuals with ART Failure in Puerto Rico. Int J Environ Res Public Health 13:ijerph13010050
Zueva, Lidia; Golubeva, Tatiana; Korneeva, Elena et al. (2016) Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency. Microsc Microanal 22:379-86
Martinez, Namyr A; Ayala, Alondra M; Martinez, Magdiel et al. (2016) Caveolin-1 Regulates the P2Y2 Receptor Signaling in Human 1321N1 Astrocytoma Cells. J Biol Chem 291:12208-22
de la Parra, Columba; Castillo-Pichardo, Linette; Cruz-Collazo, Ailed et al. (2016) Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein. Nutr Cancer 68:154-64
Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R et al. (2016) Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression. J Cancer 7:500-11
Suárez-Arroyo, Ivette J; Feliz-Mosquea, Yismeilin R; Pérez-Laspiur, Juliana et al. (2016) The proteome signature of the inflammatory breast cancer plasma membrane identifies novel molecular markers of disease. Am J Cancer Res 6:1720-40

Showing the most recent 10 out of 167 publications