Inhibition of Morphine-Potentiated HIV-1 Replication in Peripheral Blood Mononuclear Cells With the Nuclease-Resistant 2-5A Agonist Analog, 2-5AN6B
| Autor: | Ramamurthy Charubala, Thomas J. Rogers, Nancy L. Reichenbach, Amber D. Steele, Earl E. Henderson, Camille Martinand-Mari, Wolfgang Pfleiderer, Robert J. Suhadolnik, Joseph W. Homan |
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| Přispěvatelé: | Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Universität Konstanz, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE) |
| Rok vydání: | 2002 |
| Předmět: |
Narcotics
Agonist Chemokine medicine.drug_class [SDV]Life Sciences [q-bio] medicine.medical_treatment Pharmacology Virus Replication Antiviral Agents Peripheral blood mononuclear cell Interferon-gamma 03 medical and health sciences 0302 clinical medicine Interferon Endoribonucleases medicine Humans Pharmacology (medical) Interferon gamma Chemokine CCL5 Cells Cultured Chemokine CCL2 Saquinavir ComputingMilieux_MISCELLANEOUS Interferon alfa 030304 developmental biology Protein Synthesis Inhibitors 0303 health sciences Oligoribonucleotides Morphine biology Adenine Nucleotides Monocyte Interferon-alpha HIV Protease Inhibitors 3. Good health Enzyme Activation Infectious Diseases medicine.anatomical_structure Cytokine Immunology HIV-1 Leukocytes Mononuclear biology.protein Reverse Transcriptase Inhibitors Zidovudine 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Acquired Immune Deficiency Syndromes Journal of Acquired Immune Deficiency Syndromes, Lippincott, Williams & Wilkins, 2002, 30 (1), pp.9-20. ⟨10.1097/00042560-200205010-00002⟩ |
| ISSN: | 1525-4135 |
| Popis: | Opioids potentiate HIV-1 infection in vitro at least partly by suppressing immunoresponsive processes in human lymphocytes and monocytes. For example, it appears that morphine inhibits the interferon (IFN)-alpha, -beta, and -gamma-mediated natural antiviral defense pathways in human peripheral blood mononuclear cells (PBMC). In this study, we show that restoration of a key component of the antiviral pathway reverses morphine-potentiated HIV-1 infection of human PBMC. The data show that HIV-1 replication is potentiated and RNase L activity is inhibited after morphine administration. Because HIV-1 inhibits the antiviral pathway at the level of 2',5'-oligoadenylate (2-5A) synthetase and p68 kinase, antiviral enzymes that require double-stranded RNA, we overcame this blockade by the addition of the nuclease-resistant, nontoxic 2-5A agonist, 2-5A(N6B), to PBMC in culture. Addition of 2-5A(N6B), but not zidovudine or saquinavir, to morphine-treated PBMC completely reversed the morphine-induced potentiation of HIV-1 infection. Further, 2-5A(N6B) significantly enhanced expression of both IFN-alpha and IFN-gamma. Also, increased expression of IFN-gamma was associated with a significant increase in expression of RANTES and monocyte chemotactic protein (MCP)-1, chemokines that may inhibit HIV-1 infection by blocking viral attachment to CCR2 and CCR5 co-receptors. Our results suggest that reactivation of the antiviral pathway by 2-5A agonists may be useful to inhibit opioid-potentiated HIV-1 replication. |
| Databáze: | OpenAIRE |
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