title: KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression.
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.
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: R
authors.initials: R
authors.lastname: Santarelli
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Granato
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pentassuglia
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lacconi
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: M S
authors.initials: MS
authors.lastname: Gilardini Montani
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: R
authors.initials: R
authors.lastname: Gonnella
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tafani
authors.affiliation: b Istituto Pasteur-Fondazione Cenci Bolognetti , Department of Clinical and Molecular Medicine , Sapienza University of Rome , Rome , Italy.|c Azienda Ospedaliera Sant'Andrea , Rome , Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Torrisi
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cirone
mesh_terms: D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006566:Herpesviridae Infections / Q000378:metabolism / Q000473:pathology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D010766:Phosphorylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000071187:Autophagy-Related Protein 5; D015415:Biomarkers; D002135:Calcium-Binding Proteins; C033668:calpastatin; D048056:Mitogen-Activated Protein Kinase 9; D013755:Tetradecanoylphorbol Acetate
keywords: ATG5; CAPN/calpain; CAST/calpastatin; KSHV; MAPK/JNK; SQSTM1/p62; THP-1; autophagy; dendritic cells; herpesvirus; monocytes