Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype
| Autor: | Leonor Huerta, Ileana Licona-Limón, David Martínez-Méndez, Enrique Ortega, Evelyn Rivera-Toledo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Myeloid Lymphocyte Biology Jurkat cells Monocytes Immunophenotyping Cell Fusion 03 medical and health sciences Jurkat Cells Viral envelope medicine Humans Cells Cultured Monocyte Macrophages fungi env Gene Products Human Immunodeficiency Virus Cell Biology HIV envelope protein Intercellular Adhesion Molecule-1 Virology Phenotype Cell biology TLR2 030104 developmental biology medicine.anatomical_structure Carcinogens Tetradecanoylphorbol Acetate Biomarkers |
| Zdroj: | Experimental cell research. 352(1) |
| ISSN: | 1090-2422 |
| Popis: | Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4+ T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. |
| Databáze: | OpenAIRE |
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