Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells
| Autor: | Dave Bélanger, Michel J. Tremblay, Corinne Barat, Jonathan Bertin |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Gene Expression Regulation
Viral Leukotrienes Immunology Enzyme-Linked Immunosorbent Assay HIV Infections Biology Substance P Transfection Leukotriene B4 lcsh:RC346-429 Proinflammatory cytokine 03 medical and health sciences Chemokine receptor Cellular and Molecular Neuroscience 0302 clinical medicine Viral life cycle medicine Humans lcsh:Neurology. Diseases of the nervous system Neuroinflammation Cells Cultured 030304 developmental biology 0303 health sciences Microglia General Neuroscience Research Brain Flow Cytometry 3. Good health medicine.anatomical_structure Viral replication Neurology Central nervous system HIV-1 lipids (amino acids peptides and proteins) Signal transduction Viral load 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 9, Iss 1, p 55 (2012) |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/1742-2094-9-55 |
| Popis: | Background Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B4 (LTB4) and cysteinyl-leukotrienes such as LTC4 are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells. Methods To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR). Results We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C. Conclusions These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS. |
| Databáze: | OpenAIRE |
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