Abstract
We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control. The discovery of viral immune suppressive strategies that contribute to the onset and progression of viral-associated malignancies is of fundamental importance for finding new therapeutic approaches against them.
Keywords:
ATG5; CAPN/calpain; CAST/calpastatin; KSHV; MAPK/JNK; SQSTM1/p62; THP-1; autophagy; dendritic cells; herpesvirus; monocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autophagy* / drug effects
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Autophagy-Related Protein 5 / metabolism*
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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Biomarkers / metabolism
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Calcium-Binding Proteins / metabolism*
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Cell Differentiation* / drug effects
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Cell Line
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Herpesviridae Infections / metabolism
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Herpesviridae Infections / pathology
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Herpesvirus 8, Human / physiology*
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Mitogen-Activated Protein Kinase 9 / metabolism
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Monocytes / drug effects
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Monocytes / metabolism
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Monocytes / pathology*
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Monocytes / virology*
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Phosphorylation / drug effects
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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Autophagy-Related Protein 5
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Biomarkers
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Calcium-Binding Proteins
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calpastatin
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Mitogen-Activated Protein Kinase 9
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Tetradecanoylphorbol Acetate