HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 11, 10136-10141, March 12, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/11/10136    most recent M306124200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prentice, E. Articles by Denison, M. R. Search for Related Content PubMed PubMed Citation Articles by Prentice, E. Articles by Denison, M. R. Social Bookmarking                      What's this?

Coronavirus Replication Complex Formation Utilizes Components of Cellular Autophagy^*

From the Departments of ^aMicrobiology and Immunology, ⁱPediatrics, ^cPathology, and ^dCancer Biology and the ^bElizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee 37221, ^eDepartment of Cell Genetics, National Institute of Genetics, Mishima 411-8540, Japan, ^gDepartment of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan, ^hUnit Process and Combined Circuit, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, and ^fCore Research for Evolutionary Science and Technology Program, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan

The coronavirus mouse hepatitis virus (MHV) performs RNA replication on double membrane vesicles (DMVs) in the cytoplasm of the host cell. However, the mechanism by which these DMVs form has not been determined. Using genetic, biochemical, and cell imaging approaches, the role of autophagy in DMV formation and MHV replication was investigated. The results demonstrated that replication complexes co-localize with the autophagy proteins, microtubule-associated protein light-chain 3 and Apg12. MHV infection induces autophagy by a mechanism that is resistant to 3-methyladenine inhibition. MHV replication is impaired in autophagy knockout, APG5–/–, embryonic stem cell lines, but wild-type levels of MHV replication are restored by expression of Apg5 in the APG5–/–cells. In MHV-infected APG5–/–cells, DMVs were not detected; rather, the rough endoplasmic reticulum was dramatically swollen. The results of this study suggest that autophagy is required for formation of double membrane-bound MHV replication complexes and that DMV formation significantly enhances the efficiency of replication. Furthermore, the rough endoplasmic reticulum is implicated as the possible source of membranes for replication complexes.

Received for publication, June 10, 2003 , and in revised form, December 11, 2003.

^* This work was supported by Public Health Service Grant AI50083 (to M. R. D.) and National Institutes of Health Training Grant 5 T32 HL07751 in mechanisms of vascular disease (to E. P.). Experiments were performed in part through the use of the VUMC Cell Imaging Core Resource (supported by National Institutes of Health Grants CA68485 and DK20593). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^j To whom correspondence should be addressed: Dept. of Pediatrics, Vanderbilt University Medical Ctr., D6217 MCN, Nashville, TN 37232-2581. Tel.: 615-343-9881; Fax: 615-343-9723; E-mail: mark.denison{at}vanderbilt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Wang, L. M. Weiss, and A. Orlofsky Host Cell Autophagy Is Induced by Toxoplasma gondii and Contributes to Parasite Growth J. Biol. Chem., January 16, 2009; 284(3): 1694 - 1701. [Abstract] [Full Text] [PDF]

				M. Oostra, M. C. Hagemeijer, M. van Gent, C. P. J. Bekker, E. G. te Lintelo, P. J. M. Rottier, and C. A. M. de Haan Topology and Membrane Anchoring of the Coronavirus Replication Complex: Not All Hydrophobic Domains of nsp3 and nsp6 Are Membrane Spanning J. Virol., December 15, 2008; 82(24): 12392 - 12405. [Abstract] [Full Text] [PDF]

				M. Frieman and R. Baric Mechanisms of Severe Acute Respiratory Syndrome Pathogenesis and Innate Immunomodulation Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 672 - 685. [Abstract] [Full Text] [PDF]

				J. Wong, J. Zhang, X. Si, G. Gao, I. Mao, B. M. McManus, and H. Luo Autophagosome Supports Coxsackievirus B3 Replication in Host Cells J. Virol., September 15, 2008; 82(18): 9143 - 9153. [Abstract] [Full Text] [PDF]

				K. Sugimoto, M. Uema, H. Sagara, M. Tanaka, T. Sata, Y. Hashimoto, and Y. Kawaguchi Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1 J. Virol., June 1, 2008; 82(11): 5198 - 5211. [Abstract] [Full Text] [PDF]

				C. C. Posthuma, K. W. Pedersen, Z. Lu, R. G. Joosten, N. Roos, J. C. Zevenhoven-Dobbe, and E. J. Snijder Formation of the Arterivirus Replication/Transcription Complex: a Key Role for Nonstructural Protein 3 in the Remodeling of Intracellular Membranes J. Virol., May 1, 2008; 82(9): 4480 - 4491. [Abstract] [Full Text] [PDF]

				M. Ait-Goughoulte, T. Kanda, K. Meyer, J. S. Ryerse, R. B. Ray, and R. Ray Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy J. Virol., March 1, 2008; 82(5): 2241 - 2249. [Abstract] [Full Text] [PDF]

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

				D. E. Alexander, S. L. Ward, N. Mizushima, B. Levine, and D. A. Leib Analysis of the Role of Autophagy in Replication of Herpes Simplex Virus in Cell Culture J. Virol., November 15, 2007; 81(22): 12128 - 12134. [Abstract] [Full Text] [PDF]

				M. Oostra, E. G. te Lintelo, M. Deijs, M. H. Verheije, P. J. M. Rottier, and C. A. M. de Haan Localization and Membrane Topology of Coronavirus Nonstructural Protein 4: Involvement of the Early Secretory Pathway in Replication J. Virol., November 15, 2007; 81(22): 12323 - 12336. [Abstract] [Full Text] [PDF]

				N. Mizushima Autophagy: process and function Genes & Dev., November 15, 2007; 21(22): 2861 - 2873. [Abstract] [Full Text] [PDF]

				N. Jounai, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K.-Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki, et al. The Atg5 Atg12 conjugate associates with innate antiviral immune responses PNAS, August 28, 2007; 104(35): 14050 - 14055. [Abstract] [Full Text] [PDF]

				Z. Chen, Y. Wang, K. Ratia, A. D. Mesecar, K. D. Wilkinson, and S. C. Baker Proteolytic Processing and Deubiquitinating Activity of Papain-Like Proteases of Human Coronavirus NL63 J. Virol., June 1, 2007; 81(11): 6007 - 6018. [Abstract] [Full Text] [PDF]

				Y. Ye, K. Hauns, J. O. Langland, B. L. Jacobs, and B. G. Hogue Mouse Hepatitis Coronavirus A59 Nucleocapsid Protein Is a Type I Interferon Antagonist J. Virol., March 15, 2007; 81(6): 2554 - 2563. [Abstract] [Full Text] [PDF]

				C. Tangudu, H. Olivares, J. Netland, S. Perlman, and T. Gallagher Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections J. Virol., February 1, 2007; 81(3): 1220 - 1229. [Abstract] [Full Text] [PDF]

				S. R. Schaecher, J. M. Mackenzie, and A. Pekosz The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles J. Virol., January 15, 2007; 81(2): 718 - 731. [Abstract] [Full Text] [PDF]

				H. Zhou and S. Perlman Mouse Hepatitis Virus Does Not Induce Beta Interferon Synthesis and Does Not Inhibit Its Induction by Double-Stranded RNA J. Virol., January 15, 2007; 81(2): 568 - 574. [Abstract] [Full Text] [PDF]

				J.-h. Zhu, C. Horbinski, F. Guo, S. Watkins, Y. Uchiyama, and C. T. Chu Regulation of Autophagy by Extracellular Signal-Regulated Protein Kinases During 1-Methyl-4-Phenylpyridinium-Induced Cell Death Am. J. Pathol., January 1, 2007; 170(1): 75 - 86. [Abstract] [Full Text] [PDF]

				M. S. Swanson Autophagy: Eating for Good Health J. Immunol., October 15, 2006; 177(8): 4945 - 4951. [Abstract] [Full Text] [PDF]

				G. A. Versteeg, O. Slobodskaya, and W. J. M. Spaan Transcriptional profiling of acute cytopathic murine hepatitis virus infection in fibroblast-like cells J. Gen. Virol., July 1, 2006; 87(7): 1961 - 1975. [Abstract] [Full Text] [PDF]

				E. J. Snijder, Y. van der Meer, J. Zevenhoven-Dobbe, J. J. M. Onderwater, J. van der Meulen, H. K. Koerten, and A. M. Mommaas Ultrastructure and Origin of Membrane Vesicles Associated with the Severe Acute Respiratory Syndrome Coronavirus Replication Complex. J. Virol., June 1, 2006; 80(12): 5927 - 5940. [Abstract] [Full Text] [PDF]

				T. Wileman Aggresomes and autophagy generate sites for virus replication. Science, May 12, 2006; 312(5775): 875 - 878. [Abstract] [Full Text] [PDF]

				K. Ratia, K. S. Saikatendu, B. D. Santarsiero, N. Barretto, S. C. Baker, R. C. Stevens, and A. D. Mesecar Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme PNAS, April 11, 2006; 103(15): 5717 - 5722. [Abstract] [Full Text] [PDF]

				J. A. Smith, S. C. Schmechel, A. Raghavan, M. Abelson, C. Reilly, M. G. Katze, R. J. Kaufman, P. R. Bohjanen, and L. A. Schiff Reovirus Induces and Benefits from an Integrated Cellular Stress Response J. Virol., February 15, 2006; 80(4): 2019 - 2033. [Abstract] [Full Text] [PDF]

				N. Barretto, D. Jukneliene, K. Ratia, Z. Chen, A. D. Mesecar, and S. C. Baker The Papain-Like Protease of Severe Acute Respiratory Syndrome Coronavirus Has Deubiquitinating Activity J. Virol., December 15, 2005; 79(24): 15189 - 15198. [Abstract] [Full Text] [PDF]

				R. L. Graham, A. C. Sims, S. M. Brockway, R. S. Baric, and M. R. Denison The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication J. Virol., November 1, 2005; 79(21): 13399 - 13411. [Abstract] [Full Text] [PDF]

				R. R. Novoa, G. Calderita, P. Cabezas, R. M. Elliott, and C. Risco Key Golgi Factors for Structural and Functional Maturation of Bunyamwera Virus J. Virol., September 1, 2005; 79(17): 10852 - 10863. [Abstract] [Full Text] [PDF]

				C. Dye and S. G. Siddell Genomic RNA sequence of Feline coronavirus strain FIPV WSU-79/1146 J. Gen. Virol., August 1, 2005; 86(8): 2249 - 2253. [Abstract] [Full Text] [PDF]

				E. Calvo, D. Escors, J. A. Lopez, J. M. Gonzalez, A. Alvarez, E. Arza, and L. Enjuanes Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells J. Gen. Virol., August 1, 2005; 86(8): 2255 - 2267. [Abstract] [Full Text] [PDF]

				T. Shintani and D. J. Klionsky Autophagy in Health and Disease: A Double-Edged Sword Science, November 5, 2004; 306(5698): 990 - 995. [Abstract] [Full Text] [PDF]

				S. M. Brockway, X. T. Lu, T. R. Peters, T. S. Dermody, and M. R. Denison Intracellular Localization and Protein Interactions of the Gene 1 Protein p28 during Mouse Hepatitis Virus Replication J. Virol., November 1, 2004; 78(21): 11551 - 11562. [Abstract] [Full Text] [PDF]