Vaccinia virus induces apoptosis of infected macrophages
| Autor: | Zora Mělková, Mariano Esteban, Martin Vokurka, Zuzana Humlová |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Necrosis
Genes Viral bcl-X Protein Nitric Oxide Synthase Type II Apoptosis Vaccinia virus Biology Guanidines Virus Cell Line Membrane Potentials Interferon-gamma Mice Annexin Proto-Oncogene Proteins Virology Gene expression medicine Animals Macrophage Antigens Viral bcl-2-Associated X Protein DNA synthesis Macrophages Virion Molecular biology Mitochondria Nitric oxide synthase Proto-Oncogene Proteins c-bcl-2 biology.protein Nitric Oxide Synthase medicine.symptom Signal Transduction |
| Zdroj: | Scopus-Elsevier ResearcherID |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/0022-1317-83-11-2821 |
| Popis: | Vaccinia virus (VV) infects a broad range of host cells, and while it usually causes their lysis (i.e. necrosis), the nature of the cell-death phenomenon is not well understood. In this study, we show that VV induces apoptosis of cells of the murine macrophage line J774.G8, as revealed by morphological signs, DNA ladder formation, changes of mitochondrial membrane potential and annexin-V positivity. Apoptosis occurred in both untreated and IFN-γ-pretreated macrophages, and could not be inhibited by aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase. Inhibition of VV DNA synthesis and late gene expression by cytosine arabinoside also did not prevent apoptosis, while heat- or psoralen/UV-inactivated VV did not cause any apoptosis. Thus, VV early gene expression seems to be required for induction of apoptosis. At the cellular level, infection with VV induced a decrease in the levels of Bcl-xL, an anti-apoptotic member of the Bcl-2 family. The importance of loss of Bcl-xL was demonstrated by prevention of VV-mediated apoptosis on expression of Bcl-2, a functional homologue of Bcl-xL. Our findings provide evidence that induction of apoptosis by VV in macrophages requires virus early gene expression, does not involve nitric oxide, induces a decrease in mitochondrial membrane potential and is associated with altered levels of Bcl-xL. |
| Databáze: | OpenAIRE |
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