title: The activation of KSHV lytic cycle blocks autophagy in PEL cells.
abstract: This study confirms that autophagy is activated concomitantly with KSHV lytic cycle induction, and that autophagy inhibition by BECN1 knockdown reduces viral lytic gene expression. In addition, we extend previous observations and show that autophagy is blocked at late steps, during viral replication. This is indicated by the lack of colocalization of autophagosomes and lysosomes and by the LC3-II level that does not increase in the presence of bafilomycin A1in primary effusion lymphoma (PEL) cells induced to enter the lytic cycle, either by TPA/sodium butyrate (BC3 and BCBL1) or by doxycycline (TRExBCBL1-Rta). The autophagic block correlates with the downregulation of RAB7, whose silencing with specific siRNA results in an autophagic block in the same cells. Finally, by electron microscopy analysis, we observed viral particles inside autophagic vesicles in the cytoplasm of PEL cells undergoing viral replication, suggesting that they may be involved in viral transport.
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Granato
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Santarelli
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Filardi
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gonnella
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Farina
authors.affiliation: b Istituto Pasteur-Fondazione Cenci Bolognetti ; Dipartimento di Medicina Clinica e Molecolare ; Sapienza Università di Roma ; Rome , Italy.|c Azienda Ospedaliera S. Andrea ; Rome , Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: a Department of Experimental Medicine ; "Sapienza" University of Rome ; Rome , Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
keywords: KSHV; PEL; RAB7; autophagy; herpesvirus; lytic cycle