title: Hepatitis C virus present in the sera of infected patients interferes with the autophagic process of monocytes impairing their in-vitro differentiation into dendritic cells.
abstract: Autophagy has a pivotal role in the in-vitro monocyte differentiation into macrophages and dendritic cells (DCs), the most powerful antigen presenting cells (APC) with the unique capacity to initiate an adaptive immune response. Autophagy is also a mechanism by which these cells of innate immunity may degrade intracellular pathogens and mediate the antigen processing and presentation, essential to clear an infection. For these reasons, pathogens have learned how to manipulate autophagy for their own survival. In this study we found that hepatitis C virus (HCV), derived from sera of infected patients, blocked the autophagic process in differentiating monocytes, seen as LC3 II and p62 expression levels. The suppression of autophagy correlated with a reduction of cathepsins D, B and proteolytic activity, and resulted in impairment of monocyte differentiation into DCs, as indicated by the reduction of CD1a acquirement. These data suggest that the block of autophagy might be one of the underlying mechanisms of the HCV-mediated immune subversion that frequently leads to viral persistence and chronic hepatitis.
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Granato
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lacconi
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Peddis
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Di Renzo
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Valia
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University, 00161 Rome Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rivanera
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy. Electronic address: alberto.faggioni@uniroma1.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome Italy. Electronic address: mara.cirone@uniroma1.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
mesh_terms: D056704:Adaptive Immunity; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology; D002401:Cathepsin B / Q000235:genetics / Q000276:immunology; D002402:Cathepsin D / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015870:Gene Expression; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007106:Immune Sera / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*
chemical_list: D018949:Antigens, CD1; D000956:Antigens, Viral; C419393:CD1a antigen; D007106:Immune Sera; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D002401:Cathepsin B; D002402:Cathepsin D
keywords: Autophagy; Cathepsin B; Cathepsin D; Dendritic cells; HCV