Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles

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 constituen...

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Main Authors: Heike Nowag, Bruno Guhl, Kerstin Thriene, Susana Romao, Urs Ziegler, Joern Dengjel, Christian Münz
Format: Article
Language:English
Published: Elsevier 2014-12-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396414000310
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author Heike Nowag
Bruno Guhl
Kerstin Thriene
Susana Romao
Urs Ziegler
Joern Dengjel
Christian Münz
author_facet Heike Nowag
Bruno Guhl
Kerstin Thriene
Susana Romao
Urs Ziegler
Joern Dengjel
Christian Münz
author_sort Heike Nowag
collection DOAJ
description 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.
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spelling doaj.art-d0439267b0d549e2b6b54cee211801362022-12-22T02:34:05ZengElsevierEBioMedicine2352-39642014-12-011211612510.1016/j.ebiom.2014.11.007Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus ParticlesHeike Nowag0Bruno Guhl1Kerstin Thriene2Susana Romao3Urs Ziegler4Joern Dengjel5Christian Münz6Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, SwitzerlandCenter for Microscopy and Image Analysis, University of Zürich, 8057 Zürich, SwitzerlandDepartment of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7, 79104 Freiburg, GermanyViral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, SwitzerlandCenter for Microscopy and Image Analysis, University of Zürich, 8057 Zürich, SwitzerlandDepartment of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7, 79104 Freiburg, GermanyViral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, SwitzerlandEpstein 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.http://www.sciencedirect.com/science/article/pii/S2352396414000310Atg8/LC3Atg12Atg16BZLF1Lytic EBV replicationEpithelial cellB cell
spellingShingle Heike Nowag
Bruno Guhl
Kerstin Thriene
Susana Romao
Urs Ziegler
Joern Dengjel
Christian Münz
Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
EBioMedicine
Atg8/LC3
Atg12
Atg16
BZLF1
Lytic EBV replication
Epithelial cell
B cell
title Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
title_full Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
title_fullStr Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
title_full_unstemmed Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
title_short Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles
title_sort macroautophagy proteins assist epstein barr virus production and get incorporated into the virus particles
topic Atg8/LC3
Atg12
Atg16
BZLF1
Lytic EBV replication
Epithelial cell
B cell
url http://www.sciencedirect.com/science/article/pii/S2352396414000310
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