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Macroautophagy proteins assist Epstein Barr Virus production and get incorporated into the virus particles


Nowag, Heike; Guhl, Bruno; Thriene, Kerstin; Romao, Susana; Ziegler, Urs; Dengjel, Jörn; Münz, Christian (2014). Macroautophagy proteins assist Epstein Barr Virus production and get incorporated into the virus particles. EBioMedicine, 1(2-3):116-125.

Abstract

Epstein Barr virus (EBV) persists as a latent herpes virus infection in themajority of the adult human population. The virus can reactivate fromthis 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.

Abstract

Epstein Barr virus (EBV) persists as a latent herpes virus infection in themajority of the adult human population. The virus can reactivate fromthis 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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Microscopy and Image Analysis
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:13 November 2014
Deposited On:09 Dec 2014 16:29
Last Modified:23 Sep 2018 05:46
Publisher:Elsevier
ISSN:2352-3964
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ebiom.2014.11.007
Project Information:
  • : FunderSNSF
  • : Grant ID9011-051644
  • : Project TitleUlrich Bräker. Sämtliche Schriften, Band II
  • : FunderSNSF
  • : Grant ID310030_143979
  • : Project TitleMechanisms and functional relevance of macroautophagy inhibition during influenza A virus infection

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