title: Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles.
abstract: Epstein Barr virus (EBV) persists as a latent herpes virus infection in the majority of the adult human population. The virus can reactivate from this latent infection into lytic replication for virus particle production. Here, we report that autophagic membranes, which engulf cytoplasmic constituents during macroautophagy and transport them to lysosomal degradation, are stabilized by lytic EBV replication in infected epithelial and B cells. Inhibition of autophagic membrane formation compromises infectious particle production and leads to the accumulation of viral DNA in the cytosol. Vice versa, pharmacological stimulation of autophagic membrane formation enhances infectious virus production. Atg8/LC3, an essential macroautophagy protein and substrate anchor on autophagic membranes, was found in virus preparations, suggesting that EBV recruits Atg8/LC3 coupled membranes to its envelope in the cytosol. Our data indicate that EBV subverts macroautophagy and uses autophagic membranes for efficient envelope acquisition during lytic infection.
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Nowag
authors.affiliation: Center for Microscopy and Image Analysis, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guhl
authors.affiliation: Department of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany ; Freiburg Institute for Advanced Studies, University of Freiburg, Albertstr. 19, 79104 Freiburg, Germany ; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany ; ZBSA Center for Biological Systems Analysis, University of Freiburg, Habsburgerstr. 49, 79104 Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Thriene
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Susana
authors.initials: S
authors.lastname: Romao
authors.affiliation: Center for Microscopy and Image Analysis, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
authors.affiliation: Department of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany ; Freiburg Institute for Advanced Studies, University of Freiburg, Albertstr. 19, 79104 Freiburg, Germany ; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany ; ZBSA Center for Biological Systems Analysis, University of Freiburg, Habsburgerstr. 49, 79104 Freiburg, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Dengjel
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
keywords: Atg, autophagy related gene; Atg12; Atg16; Atg8/LC3; B cell; BALF1, BamH1 A fragment leftward reading frame 1; BALF4, BamH1 A fragment leftward reading frame 4; BHRF1, BamH1 H fragment rightward reading frame 1; BMRF1, BamH1 M fragment rightward reading frame 1; BNRF1, BamH1 N fragment rightward reading frame 1; BRLF1, BamH1 R fragment leftward reading frame 1; BZLF1; BZLF1, BamH1 Z fragment leftward reading frame 1; EBNA1, Epstein Barr virus nuclear antigen 1; EBV, Epstein Barr virus; Epithelial cell; LMP1, latent membrane protein 1; Lytic EBV replication; vFLIP, viral FLICE-like inhibitor protein