A Fusion Inhibitor Prevents Spread of Immunodeficiency Viruses, but Not Activation of Virus-Specific T Cells, by Dendritic Cells
| Autor: | Ines Frank, Melissa Robbiani, Hella Stössel, Irving Sivin, Agegnehu Gettie, Nikolaus Romani, J. D. Lifson, Stuart Turville, Julian W. Bess |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Time Factors T-Lymphocytes Immunology chemical and pharmacologic phenomena Biology Antiviral Agents Microbiology Virus Immune system Microscopy Electron Transmission Immunity Virology Animals Humans Cells Cultured Innate immune system HIV Dendritic Cells Dendritic cell T lymphocyte Acquired immune system Macaca mulatta Coculture Techniques HIV Envelope Protein gp41 Peptide Fragments Insect Science Pathogenesis and Immunity Female Simian Immunodeficiency Virus CD8 |
| Zdroj: | Journal of Virology. 82:5329-5339 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01987-07 |
| Popis: | Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4+T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4+, not CD8+, T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4+T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4+and CD8+T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4+T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines. |
| Databáze: | OpenAIRE |
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