The emerging roles of viroporins in ER stress response and autophagy induction during virus infection

Viruses

Volumn 7, Issue 6, 2015, Pages 2834-2857

  Fung, To Sing ^a   Torres, Jaume ^a   Liu, Ding Xiang ^a  

^a NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

Author keywords

Apoptosis; Autophagy; ER stress; UPR; Viroporin

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE; CASPASE 12; ENDOPLASMIC RETICULUM GOLGI INTERMEDIATE COMPARTMENT PROTEIN 53; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; INITIATION FACTOR 2; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 2; MAMMALIAN TARGET OF RAPAMYCIN; MICROTUBULE ASSOCIATED PROTEIN 1; NONSTRUCTURAL PROTEIN 4B; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN M2; RAP PROTEIN; ROTAVIRUS NONSTRUCTURAL PROTEIN 4; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; STRESS ACTIVATED PROTEIN KINASE; STROMAL INTERACTION MOLECULE 1; UNCLASSIFIED DRUG; VIROPORINS; VIRUS ENVELOPE PROTEIN; VIRUS PROTEIN; VIRUS SPIKE PROTEIN; PORIN; VIRAL PROTEIN;

APOPTOSIS; AUTOPHAGY; AVIAN INFECTIOUS BRONCHITIS VIRUS; CALCIUM HOMEOSTASIS; CELL MIGRATION; CELLULAR STRESS RESPONSE; ENDOPLASMIC RETICULUM STRESS; MACROAUTOPHAGY; MURINE HEPATITIS VIRUS; NONHUMAN; REVIEW; SARS CORONAVIRUS; UNFOLDED PROTEIN RESPONSE; VIRUS INFECTION; CELL MEMBRANE; ENDOPLASMIC RETICULUM; HOST PATHOGEN INTERACTION; HUMAN; METABOLISM; PHYSIOLOGICAL STRESS; PHYSIOLOGY; RNA VIRUS; VIRUS REPLICATION;

RNA VIRUSES;

AUTOPHAGY; CELL MEMBRANE; ENDOPLASMIC RETICULUM; HOST-PATHOGEN INTERACTIONS; HUMANS; PORINS; RNA VIRUSES; STRESS, PHYSIOLOGICAL; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 84930936364     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v7062749     Document Type: Review

References (134)

1. Aldabe, R.; Barco, A.; Carrasco, L. Membrane permeabilization by poliovirus proteins 2B and 2BC. J. Biol. Chem. 1996, 271, 23134–23137.
2. Pinto, L.H.; Holsinger, L.J.; Lamb, R.A. Influenza virus M2 protein has ion channel activity. Cell 1992, 69, 517–528.
3. Nieva, J.L.; Madan, V.; Carrasco, L. Viroporins: Structure and biological functions. Nat. Rev. Microbiol. 2012, 10, 563–574.
4. Hay, A.J.; Wolstenholme, A.J.; Skehel, J.J.; Smith, M.H. The molecular basis of the specific anti-influenza action of amantadine. EMBO J. 1985, 4, 3021–3024.
5. Helenius, A. Unpacking the incoming influenza virus. Cell 1992, 69, 577–578.
6. Sugrue, R.J.; Bahadur, G.; Zambon, M.C.; Hall-Smith, M.; Douglas, A.R.; Hay, A.J. Specific structural alteration of the influenza haemagglutinin by amantadine. EMBO J. 1990, 9, 3469–3476.
7. Steinmann, E.; Penin, F.; Kallis, S.; Patel, A.H.; Bartenschlager, R.; Pietschmann, T. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog. 2007, 3, e103.
8. Madan, V.; Castelló, A.; Carrasco, L. Viroporins from RNA viruses induce caspase-dependent apoptosis. Cell. Microbiol. 2008, 10, 437–451.
9. Magadán, J.G.; Bonifacino, J.S. Transmembrane domain determinants of CD4 downregulation by HIV-1 Vpu. J. Virol. 2012, 86, 757–772.
10. Iwabu, Y.; Fujita, H.; Kinomoto, M.; Kaneko, K.; Ishizaka, Y.; Tanaka, Y.; Sata, T.; Tokunaga, K. HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J. Biol. Chem. 2009, 284, 35060–35072.
11. Magadán, J.G.; Pérez-Victoria, F.J.; Sougrat, R.; Ye, Y.; Strebel, K.; Bonifacino, J.S. Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog. 2010, 6, e1000869.
12. Perez-Caballero, D.; Zang, T.; Ebrahimi, A.; McNatt, M.W.; Gregory, D.A.; Johnson, M.C.; Bieniasz, P.D. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 2009, 139, 499–511.
13. Görlach, A.; Klappa, P.; Kietzmann, T. The endoplasmic reticulum: Folding, calcium homeostasis, signaling, and redox control. Antioxid. Redox Signal. 2006, 8, 1391–1418.
14. Mekahli, D.; Bultynck, G.; Parys, J.B.; de Smedt, H.; Missiaen, L. Endoplasmic-reticulum calcium depletion and disease. Cold Spring Harb. Perspect. Biol. 2011, 3.
15. DeDiego, M.L.; Alvarez, E.; Almazán, F.; Rejas, M.T.; Lamirande, E.; Roberts, A.; Shieh, W.-J.; Zaki, S.R.; Subbarao, K.; Enjuanes, L. A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. J. Virol. 2007, 81, 1701–1713.
16. Minakshi, R.; Padhan, K.; Rani, M.; Khan, N.; Ahmad, F.; Jameel, S. The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS ONE 2009, 4, e8342.
17. Crawford, S.E.; Hyser, J.M.; Utama, B.; Estes, M.K. Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-β signaling is required for rotavirus replication. Proc. Natl. Acad. Sci. USA 2012, 109, E3405–E3413.
18. Shi, Y.; Vattem, K.M.; Sood, R.; An, J.; Liang, J.; Stramm, L.; Wek, R.C. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control.Mol. Cell. Biol. 1998, 18, 7499–7509.
19. Harding, H.P.; Novoa, I.; Zhang, Y.; Zeng, H.; Wek, R.; Schapira, M.; Ron, D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 2000, 6, 1099–1108.
20. Marciniak, S.J.; Yun, C.Y.; Oyadomari, S.; Novoa, I.; Zhang, Y.; Jungreis, R.; Nagata, K.; Harding, H.P.; Ron, D. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004, 18, 3066–3077.
21. Han, J.; Back, S.H.; Hur, J.; Lin, Y.-H.; Gildersleeve, R.; Shan, J.; Yuan, C.L.; Krokowski, D.; Wang, S.; Hatzoglou, M.; et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat. Cell Biol. 2013, 15, 481–490.
22. Yoshida, H.; Matsui, T.; Yamamoto, A.; Okada, T.; Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001, 107, 881–891.
23. Yamamoto, K.; Yoshida, H.; Kokame, K.; Kaufman, R.J.; Mori, K. Differential contributions of ATF6 and XBP1 to the activation of endoplasmic reticulum stress-responsive cis-acting elements ERSE, UPRE and ERSE-II. J. Biochem. 2004, 136, 343–350.
24. Hollien, J.; Lin, J.H.; Li, H.; Stevens, N.; Walter, P.; Weissman, J.S. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J. Cell Biol. 2009, 186, 323–331.
25. Urano, F.; Wang, X.; Bertolotti, A.; Zhang, Y.; Chung, P.; Harding, H.P.; Ron, D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000, 287, 664–666.
26. Yoneda, T.; Imaizumi, K.; Oono, K.; Yui, D.; Gomi, F.; Katayama, T.; Tohyama, M. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J. Biol. Chem. 2001, 276, 13935–13940.
27. Ye, J.; Rawson, R.B.; Komuro, R.; Chen, X.; Davé, U.P.; Prywes, R.; Brown, M.S.; Goldstein, J.L. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 2000, 6, 1355–1364.
28. Adachi, Y.; Yamamoto, K.; Okada, T.; Yoshida, H.; Harada, A.; Mori, K. ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct. Funct. 2008, 33, 75–89.
29. Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007, 8, 519–529.
30. Yang, Z.; Klionsky, D.J. Eaten alive: A history of macroautophagy. Nat. Cell Biol. 2010, 12, 814–822.
31. Kroemer, G.; Mariño, G.; Levine, B. Autophagy and the integrated stress response. Mol. Cell 2010, 40, 280–293.
32. Maiuri, M.C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. : Self-eating and self-killing Crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2007, 8, 741–752.
33. Hosokawa, N.; Hara, T.; Kaizuka, T.; Kishi, C.; Takamura, A.; Miura, Y.; Iemura, S.; Natsume, T.; Takehana, K.; Yamada, N.; et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol. Biol. Cell 2009, 20, 1981–1991.
34. Levine, B. Deretic V.; Unveiling the roles of autophagy in innate and adaptive immunity,. Nat. Rev. Immunol. 2007, 7, 767–777.
35. Mehrpour, M.; Esclatine, A.; Beau, I.; Codogno, P. Overview of macroautophagy regulation in mammalian cells. Cell Res. 2010, 20, 748–762.
36. Jheng, J.-R.; Ho, J.-Y.; Horng, J.-T. ER stress, autophagy, and RNA viruses. Front. Microbiol. 2014, 5.
37. Fung, T.S.; Huang, M.; Liu, D.X. Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions. Virus Res. 2014, 194, 110–123.
38. Watowich, S.S.; Morimoto, R.I.; Lamb, R.A. Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the GRP78-BiP gene. J. Virol. 1991, 65, 3590–3597.
39. Chan, C.-P.; Siu, K.-L.; Chin, K.-T.; Yuen, K.-Y.; Zheng, B.; Jin, D.-Y. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J. Virol. 2006, 80, 9279–9287.
40. 2+ responses. Science 1998, 280, 1763–1766.
41. Hyser, J.M.; Collinson-Pautz, M.R.; Utama, B. Estes, M.K.; Rotavirus disrupts calcium homeostasis by NSP4 viroporin activity. mBio 2010, 1.
42. Guo, H.-C.; Sun, S.-Q.; Sun, D.-H.; Wei, Y.-Q.; Xu, J.; Huang, M.; Liu, X.-T.; Liu, Z.-X.; Luo, J.-X.; Yin, H.; et al. Viroporin activity and membrane topology of classic swine fever virus p7 protein. Int. J. Biochem. Cell Biol. 2013, 45, 1186–1194.
43. Hammadi, M.; Oulidi, A.; Gackière, F.; Katsogiannou, M.; Slomianny, C.; Roudbaraki, M.; Dewailly, E.; Delcourt, P.; Lepage, G. Lotteau S.et al. ; Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: Involvement of GRP78, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2013, 27, 1600–1609.
44. Ao, D.; Guo, H.-C.; Sun, S.-Q.; Sun, D.-H.; Fung, T.S.; Wei, Y.-Q.; Han, S.-C.; Yao, X.-P.; Cao, S.-Z. Liu, D.X.; et al; Viroporin Activity of the Foot-and-Mouth disease virus non-structural 2B protein. PLoS ONE 2015, 10, e0125828.
45. Miller, S.; Krijnse-Locker, J. Modification of intracellular membrane structures for virus replication. Nat. Rev. Microbiol. 2008, 6, 363–374.
46. David-Ferreira, J.F.; Manaker, R.A. An electron microscope study of the development of a mouse hepatitis virus in tissue culture cells. J. Cell Biol. 1965, 24, 57–78.
47. Dales, S.; Eggers, H.J.; Tamm, I.; Palade, G.E. Electron microscopic study of the formation of poliovirus. Virology 1965, 26, 379–389.
48. Knoops, K.; Kikkert, M.; van den Worm, S.H.E.; Zevenhoven-Dobbe, J.C.; van der Meer, Y.; Koster, A.J.; Mommaas, A.M.; Snijder, E.J. SARS-coronavirus replicationi supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 2008, 6, e226.
49. Suhy, D.A.; Giddings, T.H. Kirkegaard, K. ; Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: An autophagy-like origin for virus-induced vesicles. J. Virol. 2000, 74, 8953–8965.
50. Prentice, E.; Jerome, W.G.; Yoshimori, T.; Mizushima, N.; Denison, M.R. Coronavirus replication complex formation utilizes components of cellular autophagy. J. Biol. Chem. 2004, 279, 10136–10141.
51. Belov, G.A.; Nair, V.; Hansen, B.T.; Hoyt, F.H.; Fischer, E.R.; Ehrenfeld, E. Complex dynamic development of poliovirus membranous replication complexes. J. Virol. 2012, 86, 302–312.
52. Reggiori, F.; Monastyrska, I.; Verheije, M.H.; Calì, T.; Ulasli, M.; Bianchi, S.; Bernasconi, R.; de Haan, C.A.M.; Molinari, M. Coronaviruses hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived erad regulators, for replication. Cell Host Microbe 2010, 7, 500–508.
53. Doedens, J.R.; Kirkegaard, K. Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. EMBO J. 1995, 14, 894–907.
54. De Jong, A.S.; Visch, H.-J.; de Mattia, F.; van Dommelen, M.M.; Swarts, H.G.; Luyten, T.; Callewaert, G.; Melchers, W.J.; Willems, P.H.; van Kuppeveld, F.J. The coxsackievirus 2B protein increases efflux of ions from the endoplasmic reticulum and Golgi, thereby inhibiting protein trafficking through the Golgi. J. Biol. Chem. 2006, 281, 14144–14150.
55. Sakaguchi, T.; Leser, G.P.; Lamb, R.A. The ion channel activity of the influenza virus M2 protein affects transport through the Golgi apparatus. J. Cell Biol. 1996, 133, 733–747.
56. Wozniak, A.L.; Griffin, S.; Rowlands, D.; Harris, M.; Yi, M.; Lemon, S.M.; Weinman, S.A. Intracellular proton conductance of the hepatitis C virus p7 protein and its contribution to infectious virus production. PLoS Pathog. 2010, 6, e1001087.
57. Sasaki, K. Yoshida, H. ; Organelle autoregulation-stress responses in the ER, Golgi, mitochondria and lysosome. J. Biochem. 2015, 157, 185–195.
58. Liu, D.X.; Inglis, S.C. Association of the infectious bronchitis virus 3c protein with the virion envelope. Virology 1991, 185, 911–917.
59. Godet, M.; L’Haridon, R.; Vautherot, J.F.; Laude, H. TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions. Virology 1992, 188, 666–675.
60. Yuan, Q.; Liao, Y.; Torres, J.; Tam, J.P.; Liu, D.X. Biochemical evidence for the presence of mixed membrane topologies of the severe acute respiratory syndrome coronavirus envelope protein expressed in mammalian cells. FEBS Lett. 2006, 580, 3192–3200.
61. Corse, E. Machamer, C.E.;. Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. J. Virol. 2000, 74, 4319–4326.
62. Liao, Y.; Yuan, Q.; Torres, J.; Tam, J.P.; Liu, D.X. Biochemical and functional characterization of the membrane association and membrane permeabilizing activity of the severe acute respiratory syndrome coronavirus envelope protein. Virology 2006, 349, 264–275.
63. Cohen, J.R.; Lin, L.D.; Machamer, C.E. Identification of a Golgi complex-targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein. J. Virol. 2011, 85, 5794–5803.
64. Raamsman, M.J.; Locker, J.K.; de Hooge, A.; de Vries, A.A.; Griffiths, G.; Vennema, H.; Rottier, P.J. Characterization of the coronavirus mouse hepatitis virus strain A59 small membrane protein E. J. Virol. 2000, 74, 2333–2342.
65. Nieto-Torres, J.L.; Dediego, M.L.; Alvarez, E.; Jiménez-Guardeño, J.M.; Regla-Nava, J.A.; Llorente, M.; Kremer, L.; Shuo, S.; Enjuanes, L. Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein. Virology 2011, 415, 69–82.
66. Maeda, J.; Repass, J.F.; Maeda, A.; Makino, S. Membrane topology of coronavirus E protein. Virology 2001, 281, 163–169.
67. Li, Y.; Surya, W.; Claudine, S.; Torres, J. Structure of a conserved Golgi complex-targeting signal in coronavirus envelope proteins. J. Biol. Chem. 2014, 289, 12535–12549.
68. Surya, W.; Li, Y.; Verdià-Bàguena, C.; Aguilella, V.M.; Torres, J. MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels. Virus Res. 2015, 201, 61–66.
69. Corse, E.; Machamer, C.E. The cytoplasmic tail of infectious bronchitis virus E protein directs Golgi targeting J. Virol. 2002, 76, 1273–1284.
70. Boscarino, J.A.; Logan, H.L.; Lacny, J.J.; Gallagher, T.M. Envelope protein palmitoylations are crucial for murine coronavirus assembly. J. Virol. 2008, 82, 2989–2999.
71. Arbely, E.; Khattari, Z.; Brotons, G.; Akkawi, M.; Salditt, T.; Arkin, I.T. A highly unusual palindromic transmembrane helical hairpin formed by SARS coronavirus E protein. J. Mol. Biol. 2004, 341, 769–779.
72. Lim, K.P.; Liu, D.X. The missing link in coronavirus assembly. Retention of the avian coronavirus infectious bronchitis virus envelope protein in the pre-Golgi compartments and physical interaction between the envelope and membrane proteins. J. Biol. Chem. 2001, 276, 17515–17523.
73. Vennema, H.; Godeke, G.J.; Rossen, J.W.; Voorhout, W.F.; Horzinek, M.C.; Opstelten, D.J.; Rottier, P.J. Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J. 1996, 15, 2020–2028.
74. Bos, E.C.; Luytjes, W.; van der Meulen, H.V.; Koerten, H.K.; Spaan, W.J. The production of recombinant infectious DI-particles of a murine coronavirus in the absence of helper virus. Virology 1996, 218, 52–60.
75. Kuo, L.; Masters, P.S. The small envelope protein E is not essential for murine coronavirus replication J. Virol. 2003, 77, 4597–4608.
76. Ortego, J.; Ceriani, J.E.; Patiño, C.; Plana, J.; Enjuanes, L. Absence of E protein arrests transmissible gastroenteritis coronavirus maturation in the secretory pathway. Virology 2007, 368, 296–308.
77. Almazán, F.; DeDiego, M.L.; Sola, I.; Zuñiga, S.; Nieto-Torres, J.L.; Marquez-Jurado, S.; Andrés, G. Enjuanes, L.; Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. mBio 2013, 4.
78. Liu, D.X.; Yuan, Q.; Liao, Y. Coronavirus envelope protein: A small membrane protein with multiple functions. Cell. Mol. Life Sci. 2007, 64, 2043–2048.
79. Wilson, L.; McKinlay, C.; Gage, P.; Ewart, G. SARS coronavirus E protein forms cation-selective ion channels. Virology 2004, 330, 322–331.
80. Wilson, L.; Gage, P.; Ewart, G. Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication. Virology 2006, 353, 294–306.
81. Verdiá-Báguena, C.; Nieto-Torres, J.L.; Alcaraz, A.; DeDiego, M.L.; Torres, J.; Aguilella, V.M.; Enjuanes, L. Coronavirus E protein forms ion channels with functionally and structurally-involved membrane lipids. Virology 2012, 432, 485–494.
82. Liao, Y.; Lescar, J.; Tam, J.P.; Liu, D.X. Expression of SARS-coronavirus envelope protein in Escherichia coli cells alters membrane permeability. Biochem. Biophys. Res. Commun. 2004, 325, 374–380.
83. Madan, V.; García Mde, J.; Sanz, M.A.; Carrasco, L. Viroporin activity of murine hepatitis virus E protein. FEBS Lett. 2005, 579, 3607–3612.
84. Pervushin, K.; Tan, E.; Parthasarathy, K.; Lin, X.; Jiang, F.L.; Yu, D.; Vararattanavech, A.; Soong, T.W.; Liu, D.X.; Torres, J. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Pathog. 2009, 5, e1000511.
85. Torres, J.; Parthasarathy, K.; Lin, X.; Saravanan, R.; Kukol, A.; Liu, D.X. Model of a putative pore: The pentameric α-helical bundle of SARS coronavirus E protein in lipid bilayers. Biophys. J. 2006, 91, 938–947.
86. Nieto-Torres, J.L.; DeDiego, M.L.; Verdiá-Báguena, C.; Jimenez-Guardeño, J.M.; Regla-Nava, J.A.; Fernandez-Delgado, R.; Castaño-Rodriguez, C.; Alcaraz, A.; Torres, J. Aguilella, V.M.; et al. ; Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog. 2014, 10, e1004077.
87. An, S.; Chen, C.-J.; Yu, X.; Leibowitz, J.L.Makino, S. ; Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. J. Virol. 1999, 73, 7853–7859.
88. Yang, Y.; Xiong, Z.; Zhang, S.; Yan, Y.; Nguyen, J.; Ng, B.; Lu, H.; Brendese, J.; Yang, F. Wang, H.; et al. ; Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors Biochem. J. 2005, 392, 135–143.
89. Ruch, T.R.; Machamer, C.E. A Single Polar Residue and Distinct Membrane Topologies impact the function of the infectious bronchitis coronavirus E protein. PLoS Pathog. 2012, 8, e1002674.
90. DeDiego, M.L.; Nieto-Torres, J.L.; Jiménez-Guardeño, J.M.; Regla-Nava, J.A.; Álvarez, E.; Oliveros, J.C.; Zhao, J.; Fett, C.; Perlman, S.; Enjuanes, L. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. PLoS Pathog. 2011, 7, e1002315.
91. Fung, T.S.; Liao, Y.; Liu, D.X. The Endoplasmic reticulum stress sensor IRE1α protects cells from apoptosis induced by the coronavirus infectious bronchitis virus. J. Virol. 2014, 88, 12752–12764.
92. Ksiazek, T.G.; Erdman, D.; Goldsmith, C.S.; Zaki, S.R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J.A. Lim W.; et al. ; A novel coronavirus associated with severe acute respiratory syndrome., N. Engl. J. Med. 2003, 348, 1953–1966.
93. Yu, C.-J.; Chen, Y.-C.; Hsiao, C.-H.; Kuo, T.-C.; Chang, S.C.; Lu, C.-Y.; Wei, W.-C.; Lee, C.-H.; Huang, L.-M. Chang, M.-F.; et al. ; Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus. FEBS Lett. 2004, 565, 111–116.
94. Yount, B.; Roberts, R.S.; Sims, A.C.; Deming, D.; Frieman, M.B.; Sparks, J.; Denison, M.R.; Davis, N.; Baric, R.S. Severe Acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice. J. Virol. 2005, 79, 14909–14922.
95. Liu, D.X.; Fung, T.S.; Chong, K.K.-L.; Shukla, A. Hilgenfeld, R. ; Accessory proteins of SARS-CoV and other coronaviruses. Antivir. Res. 2014, 109, 97–109.
96. Wang, X.; Wong, S.-M.; Liu, D.X. Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants. Nucleic Acids Res. 2006, 34, 1250–1260.
97. Ito, N.; Mossel, E.C.; Narayanan, K.; Popov, V.L.; Huang, C.; Inoue, T.; Peters, C.J.; Makino, S. Severe acute respiratory syndrome coronavirus 3a protein is a viral structural protein. J. Virol. 2005, 79, 3182–3186.
98. Oostra, M.; de Haan, C.A.; de Groot, R.J. Rottier P.J. ; Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M., J. Virol. 2006, 80, 2326–2336.
99. Tan, Y.-J.; Teng, E.; Shen, S.; Tan, T.H.P.; Goh, P.-Y.; Fielding, B.C.; Ooi, E.-E.; Tan, H.-C.; Lim, S.G.; Hong, W. A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis. J. Virol. 2004, 78, 6723–6734.
100. Lu, W.; Zheng, B.-J.; Xu, K.; Schwarz, W.; Du, L.; Wong, C.K.L.; Chen, J.; Duan, S.; Deubel, V.; Sun, B. Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release. Proc. Natl. Acad. Sci. USA 2006, 103, 12540–12545.
101. Liao, Y.; Fung, T.S.; Huang, M.; Fang, S.G.; Zhong, Y.; Liu, D.X. Upregulation of CHOP/GADD153 during coronavirus infectious bronchitis virus infection modulates apoptosis by restricting activation of the extracellular signal-regulated kinase pathway. J. Virol. 2013, 87, 8124–8134.
102. Law, P.T.W.; Wong, C.-H.; Au, T.C.C.; Chuck, C.-P.; Kong, S.-K.; Chan, P.K.S.; To, K.-F.; Lo, A.W.I.; Chan, J.Y.W. Suen Y.-K.; et al.; The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells., J. Gen. Virol. 2005, 86, 1921–1930.
103. Wong, S.L.A.; Chen, Y.; Chan, C.M.; Chan, C.S.M.; Chan, P.K.S.; Chui, Y.L.; Fung, K.P.; Waye, M.M.Y.; Tsui, S.K.W.; Chan, H.Y.E. In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila. Biochem. Biophys. Res. Commun. 2005, 337, 720–729.
104. Freundt, E.C.; Yu, L.; Goldsmith, C.S.; Welsh, S.; Cheng, A.; Yount, B.; Liu, W.; Frieman, M.B.; Buchholz, U.J. Screaton, G.R.; et al. ; The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death. J. Virol. 2010, 84, 1097–1109.
105. Ball, J.M.; Tian, P.; Zeng, C.Q.; Morris, A.P.; Estes, M.K. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science 1996, 272, 101–104.
106. Bowman, G.D.; Nodelman, I.M.; Levy, O.; Lin, S.L.; Tian, P.; Zamb, T.J.; Udem, S.A.; Venkataraghavan, B.; Schutt, C.E. Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site. J. Mol. Biol. 2000, 304, 861–871.
107. Sastri, N.P.; Viskovska, M.; Hyser, J.M.; Tanner, M.R.; Horton, L.B.; Sankaran, B.; Prasad, B.V.V.; Estes, M.K. Structural plasticity of the coiled-coil domain of rotavirus NSP4. J. Virol. 2014, 88, 13602–13612.
108. Michelangeli, F.; Ruiz, M.C.; del Castillo, J.R.; Ludert, J.E.; Liprandi, F. Effect of rotavirus infection on intracellular calcium homeostasis in cultured cells. Virology 1991, 181, 520–527.
109. Hyser, J.M.; Utama, B.; Crawford, S.E.; Broughman, J.R. Estes, M.K. ; Activation of the endoplasmic reticulum calcium sensor stim1 and store-operated calcium entry by rotavirus requires NSP4 viroporin activity. J. Virol. 2013, 87, 13579–13588.
110. Zhang, M.; Zeng, C.Q.; Morris, A.P.; Estes, M.K. A functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells. J. Virol. 2000, 74, 11663–11670.
111. Didsbury, A.; Wang, C.; Verdon, D.; Sewell, M.A.; McIntosh, J.D.; Taylor, J.A. Rotavirus NSP4 is secreted from infected cells as an oligomeric lipoprotein and binds to glycosaminoglycans on the surface of non-infected cells. Virol. J. 2011, 8, e551.
112. Berkova, Z.; Crawford, S.E.; Trugnan, G.; Yoshimori, T.; Morris, A.P.; Estes, M.K. Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms. J. Virol. 2006, 80, 6061–6071.
113. Gannagé, M.; Dormann, D.; Albrecht, R.; Dengjel, J.; Torossi, T.; Rämer, P.C.; Lee, M.; Strowig, T.; Arrey, F. Conenello, G.; et al. ; Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe 2009, 6, 367–380.
114. Beale, R.; Wise, H.; Stuart, A.; Ravenhill, B.J.; Digard, P.; Randow, F. A LC3-interacting motif in the influenza a virus M2 protein is required to subvert autophagy and maintain virion stability. Cell Host Microbe 2014, 15, 239–247.
115. Welsch, S.; Miller, S.; Romero-Brey, I.; Merz, A.; Bleck, C.K.E.; Walther, P.; Fuller, S.D.; Antony, C.; Krijnse-Locker, J.; Bartenschlager, R. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 2009, 5, 365–375.
116. Gillespie, L.K.; Hoenen, A.; Morgan, G.; Mackenzie, J.M. The endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex. J. Virol. 2010, 84, 10438–10447.
117. Roosendaal, J.; Westaway, E.G.; Khromykh, A. Mackenzie, J.M.; Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A protein. J. Virol. 2006, 80, 4623–4632.
118. Miller, S.; Kastner, S.; Krijnse-Locker, J.; Bühler, S.; Bartenschlager, R. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J. Biol. Chem. 2007, 282, 8873–8882.
119. Kaufusi, P.H.; Kelley, J.F.; Yanagihara, R.; Nerurkar, V.R. Induction of endoplasmic reticulum-derived replication-competent membrane structures by West Nile virus non-structural protein 4B. PLoS ONE 2014, 9, e84040.
120. Ambrose, R.L. Mackenzie, J.M. ; West Nile Virus differentially modulates the unfolded protein response to facilitate replication and immune evasion. J. Virol. 2011, 85, 2723–2732.
121. Ambrose, R.L.; Mackenzie, J.M. ATF6 signaling is required for efficient West Nile Virus replication by promoting cell survival and inhibition of innate immune responses. J. Virol. 2013, 87, 2206–2214.
122. Li, S.; Ye, L.; Yu, X.; Xu, B.; Li, K.; Zhu, X.; Liu, H.; Wu, X.; Kong, L. Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-κB activation. Virology 2009, 391, 257–264.
123. McLean, J.E.; Wudzinska, A.; Datan, E.; Quaglino, D.; Zakeri, Z. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J. Biol. Chem. 2011, 286, 22147–22159.
124. Blázquez, A.-B.; Martín-Acebes, M.A.; Saiz, J.-C. Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response. Front. Microbiol. 2015, 5, e797.
125. Blázquez, A.-B.; Escribano-Romero, E.; Merino-Ramos, T.; Saiz, J.-C.; Martín-Acebes, M.A. Stress responses in flavivirus-infected cells: Activation of unfolded protein response and autophagy. Front. Microbiol. 2014, 5, e266.
126. Oostra, M.; Hagemeijer, M.C.; van Gent, M.; Bekker, C.P.J.; te Lintelo, E.G.; Rottier, P.J.M.; de Haan, C.A.M. Topology and membrane anchoring of the coronavirus replication complex: Not all hydrophobic domains of NSP3 and NSP6 are Membrane Spanning. J. Virol. 2008, 82, 12392–12405.
127. Baliji, S.; Cammer, S.A.; Sobral, B.; Baker, S.C. Detection of nonstructural protein 6 in murine coronavirus-infected cells and analysis of the transmembrane topology by using bioinformatics and molecular approaches. J. Virol. 2009, 83, 6957–6962.
128. Angelini, M.M.; Akhlaghpour, M.; Neuman, B.W. Buchmeier, M.J.; Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio 2013, 4.
129. Lundin, A.; Dijkman, R.; Bergström, T.; Kann, N.; Adamiak, B.; Hannoun, C.; Kindler, E.; Jónsdóttir, H.R.; Muth, D. Kint, J.; et al. ; Targeting membrane-bound viral rna synthesis reveals potent inhibition of diverse coronaviruses including the middle east respiratory syndrome virus. PLoS Pathog. 2014, 10, e1004166.
130. Cottam, E.M.; Maier, H.J.; Manifava, M.; Vaux, L.C.; Chandra-Schoenfelder, P.; Gerner, W.; Britton, P.; Ktistakis, N.T.; Wileman, T. Coronavirus NSP6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate. Autophagy 2011, 7, 1335–1347.
131. Cottam, E.M.; Whelband, M.C.; Wileman, T. Coronavirus NSP6 restricts autophagosome expansion. Autophagy 2014, 10, 1426–1441.
132. Zhao, Z.; Thackray, L.B.; Miller, B.C.; Lynn, T.M.; Becker, M.M.; Ward, E.; Mizushima, N.N.; Denison, M.R.; Virgin, H.W. Coronavirus replication does not require the autophagy gene ATG5. Autophagy 2007, 3, 581–585.
133. Smith, J.A. A new paradigm: Innate immune sensing of viruses via the unfolded protein response. Front. Microbiol. 2014, 5, e222.
134. Levine, B.; Mizushima, N.; Virgin, H.W. Autophagy in immunity and inflammation. Nature 2011, 469, 323–335.