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

被引:84
作者
Nowag, Heike [1 ]
Guhl, Bruno [2 ]
Thriene, Kerstin [3 ,4 ,5 ,6 ]
Romao, Susana [1 ]
Ziegler, Urs [2 ]
Dengjel, Joern [3 ,4 ,5 ,6 ]
Munz, Christian [1 ]
机构
[1] Univ Zurich, Inst Expt Immunol, Viral Immunobiol, CH-8057 Zurich, Switzerland
[2] Univ Zurich, Ctr Microscopy & Image Anal, CH-8057 Zurich, Switzerland
[3] Univ Freiburg, Med Ctr, Dept Dermatol, D-79104 Freiburg, Germany
[4] Univ Freiburg, Freiburg Inst Adv Studies, D-79104 Freiburg, Germany
[5] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany
[6] Univ Freiburg, ZBSA Ctr Biol Syst Anal, D-79104 Freiburg, Germany
基金
英国医学研究理事会; 英国惠康基金; 瑞士国家科学基金会;
关键词
Atg8/LC3; Atg12; Atg16; BZLF1; Lytic EBV replication; Epithelial cell; B cell; AUTOPHAGY MACHINERY; NUCLEAR ANTIGEN; CELLS; INFECTION; COMPARTMENTS; BIOGENESIS; LIPIDATION; MOLECULES; RESPONSES; LESSONS;
D O I
10.1016/j.ebiom.2014.11.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2014 The Authors. Published by Elsevier B.V.
引用
收藏
页码:116 / 125
页数:10
相关论文
共 45 条
[1]   Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins [J].
Adhikary, D ;
Behrends, U ;
Moosmann, A ;
Witter, K ;
Bornkamm, GW ;
Mautner, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (04) :995-1006
[2]   Epstein-Barr virus provides a new paradigm: A requirement for the immediate inhibition of apoptosis [J].
Altmann, M ;
Hammerschmidt, W .
PLOS BIOLOGY, 2005, 3 (12) :2148-2157
[3]   EBV persistence in memory B cells in vivo [J].
Babcock, GJ ;
Decker, LL ;
Volk, M ;
Thorley-Lawson, DA .
IMMUNITY, 1998, 9 (03) :395-404
[4]   A LC3-Interacting Motif in the Influenza A Virus M2 Protein Is Required to Subvert Autophagy and Maintain Virion Stability [J].
Beale, Rupert ;
Wise, Helen ;
Stuart, Amanda ;
Ravenhill, Benjamin J. ;
Digard, Paul ;
Randow, Felix .
CELL HOST & MICROBE, 2014, 15 (02) :239-247
[5]   ELECTRON MICROSCOPIC STUDY OF FORMATION OF POLIOVIRUS [J].
DALES, S ;
EGGERS, HJ ;
TAMM, I ;
PALADE, GE .
VIROLOGY, 1965, 26 (03) :379-&
[6]   Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells [J].
Delecluse, HJ ;
Hilsendegen, T ;
Pich, D ;
Zeidler, R ;
Hammerschmidt, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8245-8250
[7]   The autophagy machinery is required to initiate hepatitis C virus replication [J].
Dreux, Marlene ;
Gastaminza, Pablo ;
Wieland, Stefan F. ;
Chisari, Francis V. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (33) :14046-14051
[8]   Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection [J].
English, Luc ;
Chemali, Magali ;
Duron, Johanne ;
Rondeau, Christiane ;
Laplante, Annie ;
Gingras, Diane ;
Alexander, Diane ;
Leib, David ;
Norbury, Christopher ;
Lippe, Roger ;
Desjardins, Michel .
NATURE IMMUNOLOGY, 2009, 10 (05) :480-487
[9]   VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITTS LYMPHOMA [J].
EPSTEIN, MA ;
ACHONG, BG ;
BARR, YM .
LANCET, 1964, 1 (733) :702-+
[10]   The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy [J].
Fujita, Naonobu ;
Itoh, Takashi ;
Omori, Hiroko ;
Fukuda, Mitsunori ;
Noda, Takeshi ;
Yoshimori, Tamotsu .
MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (05) :2092-2100