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Angela Alexander, S. Cai, Jinhee Kim, A. Nañez, M. Sahin, K. Maclean, K. Inoki, K. Guan, Jianjun Shen, M. Person, D. Kusewitt, G. Mills, M. Kastan, C. Walker (2010)
ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROSProceedings of the National Academy of Sciences, 107
M. Dreux, F. Chisari (2009)
Autophagy proteins promote hepatitis C virus replicationAutophagy, 5
F. Urano, Xiaozhong Wang, A. Bertolotti, Yuhong Zhang, Peter Chung, H. Harding, D. Ron (2000)
Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.Science, 287 5453
H. Yoshida, Toshie Matsui, Akira Yamamoto, T. Okada, K. Mori (2001)
XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription FactorCell, 107
X. Liang, Linda Kleeman, Hui-hui Jiang, G. Gordon, J. Goldman, G. Berry, B. Herman, Beth Levine (1998)
Protection against Fatal Sindbis Virus Encephalitis by Beclin, a Novel Bcl-2-Interacting ProteinJournal of Virology, 72
Anthony Orvedahl, B. Levine (2008)
Viral evasion of autophagyAutophagy, 4
A. Cataldi (2010)
Cell responses to oxidative stressors.Current pharmaceutical design, 16 12
A. Alexandera, Shengguan Caia, Jinhee Kima, Adrian Naneza, Mustafa Sahinc, Kirsteen MacLeand, Ken Inokie, Kun-Liang Guanf, Jian Shena, Maria Persong, Donna Kusewitta, Gordon Millsh, Michael Kastand, Cheryl Walkera (2012)
ATM signals to TSC 2 in the cytoplasm to regulate mTORC 1 in response to ROS
M. Sourisseau, C. Schilte, N. Casartelli, Céline Trouillet, F. Guivel-Benhassine, D. Rudnicka, N. Sol-Foulon, K. Roux, M. Prevost, H. Fsihi, M. Frenkiel, Fabien Blanchet, Philippe Afonso, P. Ceccaldi, S. Ozden, A. Gessain, I. Schuffenecker, B. Verhasselt, Alessia Zamborlini, A. Saïb, F. Rey, F. Arenzana‐Seisdedos, P. Desprès, A. Michault, M. Albert, O. Schwartz (2007)
Characterization of Reemerging Chikungunya VirusPLoS Pathogens, 3
M. Robinson (1955)
An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features.Transactions of the Royal Society of Tropical Medicine and Hygiene, 49 1
G. Kroemer, Guillermo Mariño, B. Levine (2010)
Autophagy and the integrated stress response.Molecular cell, 40 2
Wen-jie Guo, Si-si Ye, N. Cao, Juan Huang, Jing Gao, Qiu-Yun Chen (2010)
ROS-mediated autophagy was involved in cancer cell death induced by novel copper(II) complex.Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 62 5
Pierre-Emmanuel Joubert, G. Meiffren, I. Grégoire, G. Pontini, C. Richetta, M. Flacher, O. Azocar, P. Vidalain, M. Vidal, V. Lotteau, P. Codogno, C. Rabourdin-Combe, M. Faure (2009)
Autophagy induction by the pathogen receptor CD46.Cell host & microbe, 6 4
Pascale Krejbich-Trotot, M. Denizot, J. Hoarau, M. Jaffar-Bandjee, T. Das, P. Gasque (2011)
Chikungunya virus mobilizes the apoptotic machinery to invade host cell defensesThe FASEB Journal, 25
D. Krakauer, R. Payne (1997)
The evolution of virus–induced apoptosisProceedings of the Royal Society of London. Series B: Biological Sciences, 264
Angela Alexander, Jinhe Kim, C. Walker (2010)
ATM engages the TSC2/mTORC1 signaling node to regulate autophagyAutophagy, 6
F. Simon, H. Tolou, P. Jeandel (2006)
[The unexpected Chikungunya outbreak].La Revue de medecine interne, 27 6
N. Jounai, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K. Xin, K. Ishii, T. Kawai, S. Akira, Koichi Suzuki, K. Okuda (2007)
The Atg5–Atg12 conjugate associates with innate antiviral immune responsesProceedings of the National Academy of Sciences, 104
P. Gérardin, Vanina Guernier, J. Perrau, A. Fianu, K. Roux, P. Grivard, A. Michault, X. Lamballerie, A. Flahault, F. Favier (2008)
Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: Two methods for two critical times of the epidemicBMC Infectious Diseases, 8
Martin Uhl, Martin Uhl, O. Kepp, O. Kepp, O. Kepp, H. Jusforgues-Saklani, H. Jusforgues-Saklani, J. Vicencio, J. Vicencio, J. Vicencio, Guido Kroemer, Guido Kroemer, Guido Kroemer, Albert Ml, Albert Ml, Albert Ml (2009)
Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cellsCell Death and Differentiation, 16
Claire Calle, Pierre-Emmanuel Joubert, H. Law, M. Hasan, M. Albert (2011)
Simultaneous assessment of autophagy and apoptosis using multispectral imaging cytometryAutophagy, 7
I. Schuffenecker, I. Iteman, A. Michault, S. Murri, L. Frangeul, M. Vaney, R. Lavenir, N. Pardigon, J. Reynes, François Pettinelli, Leon Biscornet, L. Diancourt, S. Michel, S. Duquerroy, G. Guigon, M. Frenkiel, A. Brehin, Nadège Cubito, P. Desprès, F. Kunst, F. Rey, H. Zeller, S. Brisse (2006)
Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean OutbreakPLoS Medicine, 3
G. Borgherini, P. Poubeau, F. Staikowsky, M. Lory, N. Moullec, J. Becquart, Catherine Wengling, A. Michault, F. Paganin (2007)
Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 44 11
N. Danial, S. Korsmeyer (2004)
Cell Death Critical Control PointsCell, 116
C. Schilte, T. Couderc, F. Chrétien, M. Sourisseau, Nicolas Gangneux, F. Guivel-Benhassine, A. Kraxner, J. Tschopp, S. Higgs, A. Michault, F. Arenzana‐Seisdedos, M. Colonna, L. Peduto, O. Schwartz, Marc Lecuit, M. Albert (2010)
Type I IFN controls chikungunya virus via its action on nonhematopoietic cellsThe Journal of Experimental Medicine, 207
J. Jan, D. Griffin (1999)
Induction of Apoptosis by Sindbis Virus Occurs at Cell Entry and Does Not Require Virus ReplicationJournal of Virology, 73
Congcong He, M. Bassik, V. Moresi, K. Sun, Yongjie Wei, Z. Zou, Zhenyi An, Joy Loh, J. Fisher, Qihua Sun, S. Korsmeyer, M. Packer, Herman May, Joseph Hill, H. Virgin, Christopher Gilpin, Guanghua Xiao, R. Bassel-Duby, P. Scherer, B. Levine (2012)
Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasisNature, 481
Anthony Orvedahl, S. Macpherson, R. Sumpter, Z. Tallóczy, Z. Zou, B. Levine (2010)
Autophagy protects against Sindbis virus infection of the central nervous system.Cell host & microbe, 7 2
A. Thomson, H. Turnquist, G. Raimondi (2009)
Immunoregulatory functions of mTOR inhibitionNature Reviews Immunology, 9
A. Thorburn (2007)
Apoptosis and autophagy: regulatory connections between two supposedly different processesApoptosis, 13
Pascale Krejbich-Trotot, B. Gay, Ghislaine Li-Pat-Yuen, J. Hoarau, M. Jaffar-Bandjee, L. Briant, P. Gasque, M. Denizot (2011)
Chikungunya triggers an autophagic process which promotes viral replicationVirology Journal, 8
R. Zoncu, A. Efeyan, D. Sabatini (2010)
mTOR: from growth signal integration to cancer, diabetes and ageingNature Reviews Molecular Cell Biology, 12
S. Hirano (2012)
Western blot analysis.Methods in molecular biology, 926
Victoria Crotzer, J. Blum (2010)
Autophagy and adaptive immunityImmunology, 131
M. Djavaheri-Mergny, M. Djavaheri-Mergny, M. Maiuri, M. Maiuri, G. Kroemer, G. Kroemer (2010)
Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1Oncogene, 29
W. Doerfler, P. Böhm (1995)
Biology and pathogenesis
V. Deretic, B. Levine (2009)
Autophagy, immunity, and microbial adaptations.Cell host & microbe, 5 6
Anthony Orvedahl, R. Sumpter, Guanghua Xiao, Aylwin Ng, Z. Zou, Yi Tang, M. Narimatsu, Christopher Gilpin, Qihua Sun, M. Roth, C. Forst, J. Wrana, Ying Zhang, K. Luby‐Phelps, R. Xavier, Yang Xie, B. Levine (2011)
Image-Based Genome-Wide siRNA Screen Identifies Selective Autophagy FactorsNature, 480
Z. Kmietowicz (2007)
Regulator gives green light to research using human-animal embryosBMJ : British Medical Journal, 335
O. Kepp, L. Senovilla, L. Galluzzi, T. Panaretakis, F. Schlemmer, F. Madeo, L. Zitvogel, G. Kroemer (2009)
Viral subversion of immunogenic cell deathCell Cycle, 8
Yongjie Wei, S. Pattingre, Sangita Sinha, M. Bassik, B. Levine (2008)
JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy.Molecular cell, 30 6
R. Kang, H. Zeh, M. Lotze, D. Tang (2011)
The Beclin 1 network regulates autophagy and apoptosisCell Death and Differentiation, 18
D. Griffin, and Hardwick (1997)
Regulators of apoptosis on the road to persistent alphavirus infection.Annual review of microbiology, 51
Luc English, Magali Chemali, Johanne Duron, Christiane Rondeau, Annie Laplante, D. Gingras, D. Alexander, D. Leib, C. Norbury, R. Lippé, M. Desjardins (2009)
Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infectionNature Immunology, 10
J. Teodoro, P. Branton (1997)
Regulation of apoptosis by viral gene productsJournal of Virology, 71
Pierre-Emmanuel Joubert, Isabel Grégoire, G. Meiffren, C. Rabourdin-Combe, M. Faure (2011)
[Autophagy and pathogens: «Bon appétit Messieurs!»].Medecine sciences : M/S, 27 1
Am. J. Physiol. Gastrointest. Liver Physiol
E. Novo, M. Parola (2008)
Redox mechanisms in hepatic chronic wound healing and fibrogenesisFibrogenesis and Tissue Repair, 1
(1999)
) by exposure of the viral suspension to UV light (2 J over 10 min at room temperature) from UV transilluminator
P. Bodenmann, F. Althaus, B. Burnand, P. Vaucher, A. Pécoud, B. Genton (2007)
Medical care of asylum seekers: a descriptive study of the appropriateness of nurse practitioners' care compared to traditional physician-based care in a gatekeeping systemBMC Public Health, 7
I. Nakagawa, A. Amano, N. Mizushima, A. Yamamoto, H. Yamaguchi, T. Kamimoto, A. Nara, J. Funao, M. Nakata, Kayoko Tsuda, S. Hamada, T. Yoshimori (2004)
Autophagy Defends Cells Against Invading Group A StreptococcusScience, 306
Fabien Blanchet, A. Moris, Damjan Nikolic, Martin Lehmann, S. Cardinaud, R. Stalder, Eduardo Garcia, Christina Dinkins, F. Leuba, Li Wu, O. Schwartz, V. Deretic, V. Piguet (2010)
Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses.Immunity, 32 5
S. Manimunda, D. Mavalankar, T. Bandyopadhyay, A. Sugunan (2010)
Chikungunya epidemic-related mortalityEpidemiology and Infection, 139
M. Mehrpour, A. Esclatine, I. Beau, P. Codogno (2010)
Overview of macroautophagy regulation in mammalian cellsCell Research, 20
S. Ozden, M. Huerre, J. Rivière, L. Coffey, Philippe Afonso, V. Mouly, J. Monredon, J. Roger, M. Amrani, J. Yvin, M. Jaffar, M. Frenkiel, M. Sourisseau, O. Schwartz, G. Butler-Browne, P. Desprès, A. Gessain, P. Ceccaldi (2007)
Human Muscle Satellite Cells as Targets of Chikungunya Virus InfectionPLoS ONE, 2
H. Everett, Grant McFadden (1999)
Apoptosis: an innate immune response to virus infection.Trends in microbiology, 7 4
A. Powers, C. Logue (2007)
Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus.The Journal of general virology, 88 Pt 9
M. Djavaheri-Mergny, M. Amelotti, J. Mathieu, F. Besançon, C. Bauvy, P. Codogno (2007)
Regulation of Autophagy by NF-kappaB Transcription Factor and Reactives Oxygen SpeciesAutophagy, 3
Mei-Ling Li, V. Stollar (2004)
ALPHAVIRUSES AND APOPTOSISInternational Reviews of Immunology, 23
S. Inoue, K. Morita, R. Matias, J. Tuplano, R. Resuello, J. Candelario, D. Cruz, C. Mapua, F. Hasebe, A. Igarashi, F. Natividad (2003)
Distribution of three arbovirus antibodies among monkeys (Macaca fascicularis) in the PhilippinesJournal of Medical Primatology, 32
D. Vanlandingham, Konstantin Tsetsarkin, Chao Hong, K. Klingler, Kate Mcelroy, M. Lehane, S. Higgs (2005)
Development and characterization of a double subgenomic chikungunya virus infectious clone to express heterologous genes in Aedes aegypti mosqutioesInsect Biochemistry and Molecular Biology, 35
D. Vanlandingham, Konstantin Tsetsarkin, Chao Hong, K. Klingler, Kate Mcelroy, M. Lehane, S. Higgs (2005)
Development and characterization of a double subgenomic chikungunya virus infectious clone to express heterologous genes in Aedes aegypti mosquitoes.Insect biochemistry and molecular biology, 35 10
M. Kurokawa, S. Kornbluth (2010)
Stalling in mitosis and releasing the apoptotic brakeThe EMBO Journal, 29
K. Cadwell, John Liu, Sarah Brown, H. Miyoshi, Joy Loh, J. Lennerz, C. Kishi, Wumesh Kc, Javier Carrero, S. Hunt, C. Stone, E. Brunt, R. Xavier, B. Sleckman, Ellen Li, N. Mizushima, T. Stappenbeck, H. Iv (2008)
A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cellsNature, 456
Wenming Li, Qian Yang, Zixu Mao (2011)
Chaperone-mediated autophagy: machinery, regulation and biological consequencesCellular and Molecular Life Sciences, 68
J. Farrant, R. Robertson, M. Wilkins (1953)
The Mitochondrial MembraneNature, 171
M. Enserink (2006)
Massive Outbreak Draws Fresh Attention to Little-Known VirusScience, 311
N. Wilson, V. Dixit, A. Ashkenazi (2009)
Death receptor signal transducers: nodes of coordination in immune signaling networksNature Immunology, 10
Ann-Hwee Lee, N. Iwakoshi, L. Glimcher (2003)
XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein ResponseMolecular and Cellular Biology, 23
X. Zhang, J. Qu, M. Ding, X. Ren, Y. Qiu (1997)
[The mutiplication of Sindbis virus and host BHK-21 cell apoptosis].Wei sheng wu xue bao = Acta microbiologica Sinica, 37 3
G. Filomeni, Enrico Desideri, S. Cardaci, G. Rotilio, M. Ciriolo (2010)
Under the ROS: Thiol network is the principal suspect for autophagy commitmentAutophagy, 6
M. Kurokawa, S. Kornbluth (2009)
Caspases and Kinases in a Death GripCell, 138
P. Mason, A. Haddow (1957)
An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53; an additional note on Chikungunya virus isolations and serum antibodies.Transactions of the Royal Society of Tropical Medicine and Hygiene, 51 3
T. Couderc, F. Chrétien, C. Schilte, Olivier Disson, M. Brigitte, F. Guivel-Benhassine, Y. Touret, G. Barau, N. Cayet, I. Schuffenecker, P. Desprès, F. Arenzana‐Seisdedos, A. Michault, M. Albert, Marc Lecuit (2008)
A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe DiseasePLoS Pathogens, 4
O. Schwartz, M. Albert (2010)
Biology and pathogenesis of chikungunya virusNature Reviews Microbiology, 8
F. Simon, H. Tolou, P. Jeandel (2006)
Chikungunya, l'épidémie que l'on n'attendait pasRevue de Médecine Interne, 27
R. Watson (2007)
Europe witnesses first local transmission of chikungunya fever in Italy.BMJ, 335 7619
N. Yatim, M. Albert (2011)
Dying to replicate: the orchestration of the viral life cycle, cell death pathways, and immunity.Immunity, 35 4
K. Cadwell, Khushbu Patel, N. Maloney, Ta-Chiang Liu, Aylwin Ng, C. Storer, R. Head, R. Xavier, T. Stappenbeck, H. Virgin (2010)
Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in IntestineCell, 141
H. Lee, Jennifer Lund, B. Ramanathan, N. Mizushima, A. Iwasaki (2007)
Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic CellsScience, 315
G. Kroemer, L. Galluzzi, C. Brenner (2007)
Mitochondrial membrane permeabilization in cell death.Physiological reviews, 87 1
M. McGuckin, R. Eri, I. Das, R. Lourie, T. Florin (2010)
ER stress and the unfolded protein response in intestinal inflammation.American journal of physiology. Gastrointestinal and liver physiology, 298 6
L. Ng, A. Chow, Yong-Jiang Sun, D. Kwek, P. Lim, F. Dimatatac, L. Ng, E. Ooi, K. Choo, Z. Her, P. Kourilsky, Y. Leo (2009)
IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya SeverityPLoS ONE, 4
M. Gannagé, D. Dormann, R. Albrecht, J. Dengjel, T. Torossi, Patrick Rämer, Monica Lee, T. Strowig, Frida Arrey, Gina Conenello, M. Pypaert, J. Andersen, A. García-Sastre, C. Münz (2009)
Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes.Cell host & microbe, 6 4
J. Dengjel, O. Schoor, R. Fischer, Michael Reich, M. Kraus, Margret Müller, Katharina Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, R. Brock, C. Driessen, H. Rammensee, S. Stevanović (2005)
Autophagy promotes MHC class II presentation of peptides from intracellular source proteinsProceedings of the National Academy of Sciences of the United States of America, 102
Autophagy is an important survival pathway and can participate in the host response to infection. Studying Chikungunya virus (CHIKV), the causative agent of a major epidemic in India, Southeast Asia, and southern Europe, we reveal a novel mechanism by which autophagy limits cell death and mortality after infection. We use biochemical studies and single cell multispectral assays to demonstrate that direct infection triggers both apoptosis and autophagy. CHIKV-induced autophagy is mediated by the independent induction of endoplasmic reticulum and oxidative stress pathways. These cellular responses delay apoptotic cell death by inducing the IRE1α–XBP-1 pathway in conjunction with ROS-mediated mTOR inhibition. Silencing of autophagy genes resulted in enhanced intrinsic and extrinsic apoptosis, favoring viral propagation in cultured cells. Providing in vivo evidence for the relevance of our findings, Atg16L HM mice, which display reduced levels of autophagy, exhibited increased lethality and showed a higher sensitivity to CHIKV-induced apoptosis. Based on kinetic studies and the observation that features of apoptosis and autophagy were mutually exclusive, we conclude that autophagy inhibits caspase-dependent cell death but is ultimately overwhelmed by viral replication. Our study suggests that inducers of autophagy may limit the pathogenesis of acute Chikungunya disease. Submitted: 17 May 2011 Accepted: 19 March 2012 This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ).
The Journal of Experimental Medicine – Rockefeller University Press
Published: May 7, 2012
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