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Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells

Science, 9 March 2007
Vol. 315, Issue 5817, p. 1398-1401
DOI: 10.1126/science.1136880

Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells

  1. Heung Kyu Lee1,*,
  2. Jennifer M. Lund1,*,,
  3. Balaji Ramanathan1,*,
  4. Noboru Mizushima2,3,
  5. Akiko Iwasaki1,
  1. 1 Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
  2. 2 Department of Cell Physiology, Tokyo Medical and Dental University, Graduate School and Faculty of Medicine, Tokyo, Japan.
  3. 3 Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan.
  1. To whom correspondence should be addressed: akiko.iwasaki{at}yale.edu
  • * These authors contributed equally to this work.

  • Present address: Department of Immunology, University of Washington, Seattle, WA.

Abstract

Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-α by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-α secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.

    • Received for publication 30 October 2006.
    • Accepted for publication 17 January 2007.

    Citation:

    H. K. Lee, J. M. Lund, B. Ramanathan, N. Mizushima, and A. Iwasaki, Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells. Science 315, 1398-1401 (2007).

    Activation and Regulation of DNA-Driven Immune Responses
    S. R. Paludan
    Microbiol. Mol. Biol. Rev. 79, 225-241 (29 April 2015)

    Viral entry route determines how human plasmacytoid dendritic cells produce type I interferons
    D. Bruni, M. Chazal, L. Sinigaglia, L. Chauveau, O. Schwartz, P. Despres, and N. Jouvenet
    Sci Signal 8, ra25-ra25 (3 March 2015)

    Emerging Principles Governing Signal Transduction by Pattern-Recognition Receptors
    J. C. Kagan, and G. M. Barton
    Cold Spring Harb. Perspect. Biol. 7, a016253-a016253 (1 March 2015)

    The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon
    W. A. Grimm, J. S. Messer, S. F. Murphy, T. Nero, J. P. Lodolce, C. R. Weber, M. F. Logsdon, S. Bartulis, B. E. Sylvester, A. Springer et al.
    Gut 0, gutjnl-2014-308735v1-gutjnl-2014-308735 (2 February 2015)

    Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid Sensors
    S. Pandey, T. Kawai, and S. Akira
    Cold Spring Harb. Perspect. Biol. 7, a016246-a016246 (1 January 2015)

    Sensing the hybrid--a novel PAMP for TLR9
    S. B. Jensen, and S. R. Paludan
    EMBO J. 33, 529-530 (18 March 2014)

    RNA:DNA hybrids are a novel molecular pattern sensed by TLR9
    R. E. Rigby, L. M. Webb, K. J. Mackenzie, Y. Li, A. Leitch, M. A. M. Reijns, R. J. Lundie, A. Revuelta, D. J. Davidson, S. Diebold et al.
    EMBO J. 33, 542-558 (18 March 2014)

    Attenuation of Respiratory Syncytial Virus-Induced and RIG-I-Dependent Type I IFN Responses in Human Neonates and Very Young Children
    N. Marr, T.-I. Wang, S. H. Y. Kam, Y. S. Hu, A. A. Sharma, A. Lam, J. Markowski, A. Solimano, P. M. Lavoie, S. E. Turvey et al.
    J. Immunol. 192, 948-957 (1 February 2014)

    Autophagy facilitates cytokine-induced ICAM-1 expression
    C.-Y. Wang, T.-H. Chiang, C.-L. Chen, P.-C. Tseng, S.-Y. Chien, Y.-J. Chuang, T.-T. Yang, C.-Y. Hsieh, P.-C. Choi, C.-F. Lin et al.
    Innate Immunity 20, 200-213 (1 February 2014)

    The plasmacytoid dendritic cell: at the cross-roads in asthma
    J. P. Lynch, S. B. Mazzone, M. J. Rogers, J. J. Arikkatt, Z. Loh, A. L. Pritchard, J. W. Upham, and S. Phipps
    Eur Respir J 43, 264-275 (1 January 2014)

    Mechanism and Physiological Significance of Growth Factor-Related Autophagy
    T. Y. Li, S.-Y. Lin, and S.-C. Lin
    Physiology 28, 423-431 (1 November 2013)

    Autophagy-Inducing Protein Beclin-1 in Dendritic Cells Regulates CD4 T Cell Responses and Disease Severity during Respiratory Syncytial Virus Infection
    M. Reed, S. H. Morris, S. Jang, S. Mukherjee, Z. Yue, and N. W. Lukacs
    J. Immunol. 191, 2526-2537 (1 September 2013)

    Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology
    Y. Cheng, X. Ren, W. N. Hait, and J.-M. Yang
    Pharmacol. Rev. 65, 1162-1197 (13 August 2013)

    Human placental trophoblasts confer viral resistance to recipient cells
    E. Delorme-Axford, R. B. Donker, J.-F. Mouillet, T. Chu, A. Bayer, Y. Ouyang, T. Wang, D. B. Stolz, S. N. Sarkar, A. E. Morelli et al.
    Proc. Natl. Acad. Sci. USA 110, 12048-12053 (16 July 2013)

    TLR7 Negatively Regulates Dendrite Outgrowth through the Myd88-c-Fos-IL-6 Pathway
    H.-Y. Liu, Y.-F. Hong, C.-M. Huang, C.-Y. Chen, T.-N. Huang, and Y.-P. Hsueh
    J. Neurosci. 33, 11479-11493 (10 July 2013)

    A Proautophagic Antiviral Role for the Cellular Prion Protein Identified by Infection with a Herpes Simplex Virus 1 ICP34.5 Mutant
    M. Korom, K. M. Wylie, H. Wang, K. L. Davis, M. S. Sangabathula, G. S. DeLassus, and L. A. Morrison
    J. Virol. 87, 5882-5894 (15 May 2013)

    Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors
    X. He, H. Jia, Z. Jing, and D. Liu
    Acta Biochim Biophys Sin 45, 241-258 (1 April 2013)

    Self-eating and self-defense: autophagy controls innate immunity and adaptive immunity
    G. Liu, Y. Bi, R. Wang, and X. Wang
    J. Leukoc. Biol. 93, 511-519 (1 April 2013)

    Active Escape of Orientia tsutsugamushi from Cellular Autophagy
    Y. Ko, J.-H. Choi, N.-Y. Ha, I.-S. Kim, N.-H. Cho, and M.-S. Choi
    Infect. Immun. 81, 552-559 (1 February 2013)

    Autophagy and selective deployment of Atg proteins in antiviral defense
    B. Yordy, M. C. Tal, K. Hayashi, O. Arojo, and A. Iwasaki
    Int Immunol 25, 1-10 (1 January 2013)

    Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
    E. F. Castillo, A. Dekonenko, J. Arko-Mensah, M. A. Mandell, N. Dupont, S. Jiang, M. Delgado-Vargas, G. S. Timmins, D. Bhattacharya, H. Yang et al.
    Proc. Natl. Acad. Sci. USA 109, E3168-E3176 (13 November 2012)

    Regulation of Inflammatory Response by 3-Methyladenine Involves the Coordinative Actions on Akt and Glycogen Synthase Kinase 3{beta} Rather than Autophagy
    Y.-C. Lin, H.-C. Kuo, J.-S. Wang, and W.-W. Lin
    J. Immunol. 189, 4154-4164 (15 October 2012)

    RNase L Triggers Autophagy in Response to Viral Infections
    A. Chakrabarti, P. K. Ghosh, S. Banerjee, C. Gaughan, and R. H. Silverman
    J. Virol. 86, 11311-11321 (15 October 2012)

    Autophagic Clearance of Sin Nombre Hantavirus Glycoprotein Gn Promotes Virus Replication in Cells
    I. T. M. Hussein, E. Cheng, S. S. Ganaie, M. J. Werle, S. Sheema, A. Haque, and M. A. Mir
    J. Virol. 86, 7520-7529 (15 July 2012)

    Autophagy: An Emerging Immunological Paradigm
    V. Deretic, E. Cheng, S. S. Ganaie, M. J. Werle, S. Sheema, A. Haque, and M. A. Mir
    J. Immunol. 189, 15-20 (1 July 2012)

    An Astrocyte-Specific Proteomic Approach to * Inflammatory Responses in Experimental Rat Glaucoma
    G. Tezel, X. Yang, C. Luo, J. Cai, and D. W. Powell
    IOVS 53, 4220-4233 (28 June 2012)

    Chikungunya virus-induced autophagy delays caspase-dependent cell death
    P.-E. Joubert, S. W. Werneke, C. de la Calle, F. Guivel-Benhassine, A. Giodini, L. Peduto, B. Levine, O. Schwartz, D. J. Lenschow, M. L. Albert et al.
    JEM 209, 1029-1047 (7 May 2012)

    Failure of innate and adaptive immune responses in controlling hepatitis C virus infection
    R. Thimme, M. Binder, and R. Bartenschlager
    FEMS Microbiol Rev 36, 663-683 (1 May 2012)

    Production of Interferon {alpha} by Human Immunodeficiency Virus Type 1 in Human Plasmacytoid Dendritic Cells Is Dependent on Induction of Autophagy
    D. Zhou, K. H. Kang, and S. A. Spector
    The Journal of Infectious Disease 205, 1258-1267 (15 April 2012)

    The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells
    L. Li, L. Wang, R. Xiao, G. Zhu, Y. Li, C. Liu, R. Yang, Z. Tang, J. Li, W. Huang et al.
    Biosci. Rep. 32, 171-184 (1 April 2012)

    Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion
    S. Jensen, and A. R. Thomsen
    J. Virol. 86, 2900-2910 (15 March 2012)

    The Role of Toll-like Receptors in Age-Associated Lung Diseases
    M. Volkova, Y. Zhang, A. C. Shaw, and P. J. Lee
    J Gerontol A Biol Sci Med Sci 0, glr226v1-glr226 (5 March 2012)

    Genetic Inactivation of COPI Coatomer Separately Inhibits Vesicular Stomatitis Virus Entry and Gene Expression
    D. K. Cureton, R. Burdeinick-Kerr, and S. P. J. Whelan
    J. Virol. 86, 655-666 (15 January 2012)

    MyD88 Interacts with Interferon Regulatory Factor (IRF) 3 and IRF7 in Atlantic Salmon (Salmo salar): TRANSGENIC SsMyD88 MODULATES THE IRF-INDUCED TYPE I INTERFERON RESPONSE AND ACCUMULATES IN AGGRESOMES
    D. B. Iliev, M. Sobhkhez, K. Fremmerlid, and J. B. Jorgensen
    J Biol Chem 286, 42715-42724 (9 December 2011)

    Activation of Autophagy by {alpha}-Herpesviruses in Myeloid Cells Is Mediated by Cytoplasmic Viral DNA through a Mechanism Dependent on Stimulator of IFN Genes
    S. B. Rasmussen, K. A. Horan, C. K. Holm, A. J. Stranks, T. C. Mettenleiter, A. K. Simon, S. B. Jensen, F. J. Rixon, B. He, S. R. Paludan et al.
    J. Immunol. 187, 5268-5276 (15 November 2011)

    Autophagy-Mediated Dendritic Cell Activation Is Essential for Innate Cytokine Production and APC Function with Respiratory Syncytial Virus Responses
    S. Morris, M. S. Swanson, A. Lieberman, M. Reed, Z. Yue, D. M. Lindell, and N. W. Lukacs
    J. Immunol. 187, 3953-3961 (15 October 2011)

    Myxoma Virus Induces Type I Interferon Production in Murine Plasmacytoid Dendritic Cells via a TLR9/MyD88-, IRF5/IRF7-, and IFNAR-Dependent Pathway
    P. Dai, H. Cao, T. Merghoub, F. Avogadri, W. Wang, T. Parikh, C.-M. Fang, P. M. Pitha, K. A. Fitzgerald, M. M. Rahman et al.
    J. Virol. 85, 10814-10825 (15 October 2011)

    TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes
    M. Swiecki, S. A. McCartney, Y. Wang, and M. Colonna
    J. Leukoc. Biol. 90, 691-701 (1 October 2011)

    Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells
    T. Imai, Y. Kato, C. Kajiwara, S. Mizukami, I. Ishige, T. Ichiyanagi, M. Hikida, J.-Y. Wang, and H. Udono
    Proc. Natl. Acad. Sci. USA 108, 16363-16368 (27 September 2011)

    TLR4 Engagement during TLR3-Induced Proinflammatory Signaling in Dendritic Cells Promotes IL-10-Mediated Suppression of Antitumor Immunity
    D. Bogunovic, O. Manches, E. Godefroy, A. Yewdall, A. Gallois, A. M. Salazar, I. Marie, D. E. Levy, and N. Bhardwaj
    Cancer Res. 71, 5467-5476 (15 August 2011)

    Gammaherpesvirus 68 Infection of Endothelial Cells Requires both Host Autophagy Genes and Viral Oncogenes for Optimal Survival and Persistence
    A. L. Suarez, R. Kong, T. George, L. He, Z. Yue, and L. F. van Dyk
    J. Virol. 85, 6293-6308 (1 July 2011)

    Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population
    X.-j. Zhou, X.-l. Lu, J.-c. Lv, H.-z. Yang, L.-x. Qin, M.-h. Zhao, Y. Su, Z.-g. Li, and H. Zhang
    Ann Rheum Dis 70, 1330-1337 (1 July 2011)

    Oncolytic Vesicular Stomatitis Virus Induces Apoptosis in U87 Glioblastoma Cells by a Type II Death Receptor Mechanism and Induces Cell Death and Tumor Clearance In Vivo
    Z. D. Cary, M. C. Willingham, and D. S. Lyles
    J. Virol. 85, 5708-5717 (15 June 2011)

    Plasmacytoid Dendritic Cells Promote Host Defense against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway
    S. Davidson, G. Kaiko, Z. Loh, A. Lalwani, V. Zhang, K. Spann, S. Y. Foo, N. Hansbro, S. Uematsu, S. Akira et al.
    J. Immunol. 186, 5938-5948 (15 May 2011)

    Temporal Regulation of Intracellular Organelle Homeostasis in T Lymphocytes by Autophagy
    W. Jia, and Y.-W. He
    J. Immunol. 186, 5313-5322 (1 May 2011)

    Autophagy Regulates Endoplasmic Reticulum Homeostasis and Calcium Mobilization in T Lymphocytes
    W. Jia, H. H. Pua, Q.-J. Li, and Y.-W. He
    J. Immunol. 186, 1564-1574 (1 February 2011)

    Regulation of Mammalian Autophagy in Physiology and Pathophysiology
    B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-Arencibia, Z. W. Green-Thompson, M. Jimenez-Sanchez, V. I. Korolchuk, M. Lichtenberg, S. Luo et al.
    Physiol. Rev. 90, 1383-1435 (1 October 2010)

    Autophagy Facilitates IFN-{gamma}-induced Jak2-STAT1 Activation and Cellular Inflammation
    Y.-P. Chang, C.-C. Tsai, W.-C. Huang, C.-Y. Wang, C.-L. Chen, Y.-S. Lin, J.-I. Kai, C.-Y. Hsieh, Y.-L. Cheng, P.-C. Choi et al.
    J Biol Chem 285, 28715-28722 (10 September 2010)

    Regulation of innate immune responses by autophagy-related proteins
    T. Saitoh, and S. Akira
    JCB 189, 925-935 (14 June 2010)

    Plasmacytoid dendritic cells in HIV infection: striking a delicate balance
    P. Fitzgerald-Bocarsly, and E. S. Jacobs
    J. Leukoc. Biol. 87, 609-620 (1 April 2010)

    Cell Type-Specific Recognition of Human Metapneumoviruses (HMPVs) by Retinoic Acid-Inducible Gene I (RIG-I) and TLR7 and Viral Interference of RIG-I Ligand Recognition by HMPV-B1 Phosphoprotein
    N. Goutagny, Z. Jiang, J. Tian, P. Parroche, J. Schickli, B. G. Monks, N. Ulbrandt, H. Ji, P. A. Kiener, A. J. Coyle et al.
    J. Immunol. 184, 1168-1179 (1 February 2010)

    Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response
    T. Saitoh, N. Fujita, T. Hayashi, K. Takahara, T. Satoh, H. Lee, K. Matsunaga, S. Kageyama, H. Omori, T. Noda et al.
    Proc. Natl. Acad. Sci. USA 106, 20842-20846 (8 December 2009)

    Morbus Crohn--a disease of failing macroautophagy in the immune system?
    S. Meixlsperger, and C. Munz
    Int Immunol 21, 1205-1211 (1 November 2009)

    Toll-Like Receptor 3 Mediates Establishment of an Antiviral State against Hepatitis C Virus in Hepatoma Cells
    N. Wang, Y. Liang, S. Devaraj, J. Wang, S. M. Lemon, and K. Li
    J. Virol. 83, 9824-9834 (1 October 2009)

    Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages
    G. B. Kyei, C. Dinkins, A. S. Davis, E. Roberts, S. B. Singh, C. Dong, L. Wu, E. Kominami, T. Ueno, A. Yamamoto et al.
    JCB 186, 255-268 (27 July 2009)

    Pathogen recognition in the innate immune response
    H. Kumar, T. Kawai, and S. Akira
    Biochem. J. 420, 1-16 (15 May 2009)

    Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses
    S. Tluk, M. Jurk, A. Forsbach, R. Weeratna, U. Samulowitz, A. M. Krieg, S. Bauer, and J. Vollmer
    Int Immunol 21, 607-619 (1 May 2009)

    The roles of TLRs, RLRs and NLRs in pathogen recognition
    T. Kawai, and S. Akira
    Int Immunol 21, 317-337 (1 April 2009)

    Cutting Edge: TLR-Dependent Viral Recognition Along with Type I IFN Positive Feedback Signaling Masks the Requirement of Viral Replication for IFN-{alpha} Production in Plasmacytoid Dendritic Cells
    Y. Kumagai, H. Kumar, S. Koyama, T. Kawai, O. Takeuchi, and S. Akira
    J. Immunol. 182, 3960-3964 (1 April 2009)

    Autophagy and Its Role in MHC-Mediated Antigen Presentation
    V. L. Crotzer, and J. S. Blum
    J. Immunol. 182, 3335-3341 (15 March 2009)

    Developmental regulation of MHC II expression and transport in human plasmacytoid-derived dendritic cells
    C. Sadaka, M.-A. Marloie-Provost, V. Soumelis, and P. Benaroch
    Blood 113, 2127-2135 (5 March 2009)

    Hantaan Virus Triggers TLR3-Dependent Innate Immune Responses
    W. Handke, R. Oelschlegel, R. Franke, D. H. Kruger, and A. Rang
    J. Immunol. 182, 2849-2858 (1 March 2009)

    Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
    M. C. Tal, M. Sasai, H. K. Lee, B. Yordy, G. S. Shadel, and A. Iwasaki
    Proc. Natl. Acad. Sci. USA 106, 2770-2775 (24 February 2009)

    Measles Virus V Protein Is a Decoy Substrate for I{kappa}B Kinase {alpha} and Prevents Toll-Like Receptor 7/9-Mediated Interferon Induction
    C. K. Pfaller, and K.-K. Conzelmann
    J. Virol. 82, 12365-12373 (15 December 2008)

    Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis
    R. J Xavier, A. Huett, and J. D Rioux
    Gut 57, 717-720 (1 June 2008)

    Analysis of the Neuroinflammatory Response to TLR7 Stimulation in the Brain: Comparison of Multiple TLR7 and/or TLR8 Agonists
    N. B. Butchi, S. Pourciau, M. Du, T. W. Morgan, and K. E. Peterson
    J. Immunol. 180, 7604-7612 (1 June 2008)

    Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection
    N. Zucchini, G. Bessou, S. Traub, S. H. Robbins, S. Uematsu, S. Akira, L. Alexopoulou, and M. Dalod
    J. Immunol. 180, 5799-5803 (1 May 2008)

    Plasmacytoid Dendritic Cells Are Activated by Toxoplasma gondii to Present Antigen and Produce Cytokines
    M. Pepper, F. Dzierszinski, E. Wilson, E. Tait, Q. Fang, F. Yarovinsky, T. M. Laufer, D. Roos, and C. A. Hunter
    J. Immunol. 180, 6229-6236 (1 May 2008)

    Toll-like receptors control autophagy
    M. A. Delgado, R. A. Elmaoued, A. S. Davis, G. Kyei, and V. Deretic
    EMBO J. 27, 1110-1121 (9 April 2008)

    PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation
    C. Guiducci, C. Ghirelli, M.-A. Marloie-Provost, T. Matray, R. L. Coffman, Y.-J. Liu, F. J. Barrat, and V. Soumelis
    JEM 205, 315-322 (18 February 2008)

    Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures
    R. E. Randall, and S. Goodbourn
    J. Gen. Virol. 89, 1-47 (1 January 2008)

    Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells
    M. C. Silva, A. Guerrero-Plata, F. D. Gilfoy, R. P. Garofalo, and P. W. Mason
    J. Virol. 81, 13640-13648 (15 December 2007)

    Autophagy: process and function
    N. Mizushima, A. Guerrero-Plata, F. D. Gilfoy, R. P. Garofalo, and P. W. Mason
    Genes Dev. 21, 2861-2873 (15 November 2007)

    The Atg5 Atg12 conjugate associates with innate antiviral immune responses
    N. Jounai, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K.-Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki et al.
    Proc. Natl. Acad. Sci. USA 104, 14050-14055 (28 August 2007)

    Private Lives: Reflections and Challenges in Understanding the Cell Biology of the Immune System
    I. Mellman, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K.-Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki et al.
    Science 317, 625-627 (3 August 2007)

    IMMUNOLOGY: Eating In to Avoid Infection
    C. Reis e Sousa, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K.-Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki et al.
    Science 315, 1376-1377 (9 March 2007)

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