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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Format: | Article |
Language: | English |
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Elsevier
2014-12-01
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Series: | EBioMedicine |
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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. |
first_indexed | 2024-04-13T19:01:40Z |
format | Article |
id | doaj.art-d0439267b0d549e2b6b54cee21180136 |
institution | Directory Open Access Journal |
issn | 2352-3964 |
language | English |
last_indexed | 2024-04-13T19:01:40Z |
publishDate | 2014-12-01 |
publisher | Elsevier |
record_format | Article |
series | EBioMedicine |
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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