The PERK arm of the unfolded protein response negatively regulates transmissible gastroenteritis virus replication by suppressing protein translation and promoting type I interferon production

Journal of Virology

Volumn 92, Issue 15, 2018, Pages

  Xue, Mei ^a   Fu, Fang ^a   Ma, Yanlong ^a   Zhang, Xin ^a   Li, Liang ^a   Feng, Li ^a   Liu, Pinghuang ^a  

^a INSTITUTE OF PLANT PROTECTION   (China)

Author keywords

Endoplasmic reticulum stress; Interferon; Protein kinase R like ER kinase; Translation attenuation; Transmissible gastroenteritis virus; Unfolded protein response

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; ALPHA INTERFERON; BETA INTERFERON; GLUCOSE REGULATED PROTEIN 78; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INITIATION FACTOR 2ALPHA; INTERFERON; PROTEIN KINASE R LIKE ER KINASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VIRAL PROTEIN; INITIATION FACTOR 2; PERK KINASE; PROTEIN KINASE R;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; CORONAVIRIDAE INFECTION; ENDOPLASMIC RETICULUM STRESS; IN VITRO STUDY; IN VIVO STUDY; INTERFERON PRODUCTION; MALE; NONHUMAN; PIGLET; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN TARGETING; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TESTICULAR CELL LINE; TRANSMISSIBLE GASTROENTERITIS VIRUS; UNFOLDED PROTEIN RESPONSE; UPREGULATION; VIRUS REPLICATION; VIRUS TITRATION; ANIMAL; BIOSYNTHESIS; CELL LINE; GENETICS; METABOLISM; PHYSIOLOGY; PIG; PROTEIN SYNTHESIS;

ACTIVATING TRANSCRIPTION FACTOR 6; ANIMALS; CELL LINE; EIF-2 KINASE; EUKARYOTIC INITIATION FACTOR-2; INTERFERON TYPE I; PROTEIN BIOSYNTHESIS; SWINE; TRANSMISSIBLE GASTROENTERITIS VIRUS; UNFOLDED PROTEIN RESPONSE; VIRUS REPLICATION;

EID: 85050142311     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00431-18     Document Type: Article

References (101)

1. Hetz C, Papa FR. 2018. The unfolded protein response and cell fate control. Mol Cell 69:169-181. https://doi.org/10.1016/j.molcel.2017.06.017
2. Fung TS, Huang M, Liu DX. 2014. Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions. Virus Res 194:110-123. https://doi.org/10.1016/j.virusres.2014.09.016
3. Ron D, Walter P. 2007. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519-529. https://doi.org/10.1038/nrm2199
4. Credle JJ, Finer-Moore JS, Papa FR, Stroud RM, Walter P. 2005. On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc Natl Acad Sci U S A 102:18773-18784. https://doi.org/10.1073/pnas.0509487102
5. Karagoz GE, Acosta-Alvear D, Nguyen HT, Lee CP, Chu F, Walter P. 2017. An unfolded protein-induced conformational switch activates mammalian IRE1. Elife 6:e30700. https://doi.org/10.7554/eLife.30700
6. Pincus D, Chevalier MW, Aragon T, van Anken E, Vidal SE, El-Samad H, Walter P. 2010. BiP binding to the ER-stress sensor Ire1 tunes the homeostatic behavior of the unfolded protein response. PLoS Biol 8:e1000415. https://doi.org/10.1371/journal.pbio.1000415
7. Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC. 1998. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol 18:7499-7509. https://doi.org/10.1128/MCB.18.12.7499
8. Pavio N, Romano PR, Graczyk TM, Feinstone SM, Taylor DR. 2003. Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK. J Virol 77:3578-3585. https://doi.org/10.1128/ JVI.77.6.3578-3585.2003
9. Wek RC, Jiang HY, Anthony TG. 2006. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34:7-11. https://doi.org/10.1042/BST0340007
10. Gosert R, Kanjanahaluethai A, Egger D, Bienz K, Baker SC. 2002. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J Virol 76:3697-3708. https://doi.org/10.1128/JVI.76.8.3697-3708.2002
11. Gallagher T, Perlman S. 2013. Public health: broad reception for coronavirus. Nature 495:176-177. https://doi.org/10.1038/495176a
12. Fung TS, Liu DX. 2014. Coronavirus infection, ER stress, apoptosis and innate immunity. Front Microbiol 5:296. https://doi.org/10.3389/fmicb.2014.00296
13. Chan CP, Siu KL, Chin KT, Yuen KY, Zheng B, Jin DY. 2006. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J Virol 80:9279-9287. https://doi.org/10.1128/ JVI.00659-06
14. Snijder EJ, van der Meer Y, Zevenhoven-Dobbe J, Onderwater JJ, van der Meulen J, Koerten HK, Mommaas AM. 2006. Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex. J Virol 80:5927-5940. https:// doi.org/10.1128/JVI.02501-05
15. Perlman S, Netland J. 2009. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 7:439-450. https://doi.org/ 10.1038/nrmicro2147
16. Masters PS. 2006. The molecular biology of coronaviruses. Adv Virus Res 66:193-292. https://doi.org/10.1016/S0065-3527(06)66005-3
17. Versteeg GA, van de Nes PS, Bredenbeek PJ, Spaan WJ. 2007. The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. J Virol 81:10981-10990. https://doi.org/10.1128/JVI.01033-07
18. Liao Y, Fung TS, Huang M, Fang SG, Zhong Y, Liu DX. 2013. Upregulation of CHOP/GADD153 during coronavirus infectious bronchitis virus infection modulates apoptosis by restricting activation of the extracellular signal-regulated kinase pathway. J Virol 87:8124-8134. https://doi.org/ 10.1128/JVI.00626-13
19. DeDiego ML, Nieto-Torres JL, Jimenez-Guardeno JM, Regla-Nava JA, Alvarez E, Oliveros JC, Zhao J, Fett C, Perlman S, Enjuanes L. 2011. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. PLoS Pathog 7:e1002315. https://doi.org/ 10.1371/journal.ppat.1002315
20. Krahling V, Stein DA, Spiegel M, Weber F, Muhlberger E. 2009. Severe acute respiratory syndrome coronavirus triggers apoptosis via protein kinase R but is resistant to its antiviral activity. J Virol 83:2298-2309. https://doi.org/10.1128/JVI.01245-08
21. Datan E, Roy SG, Germain G, Zali N, McLean JE, Golshan G, Harbajan S, Lockshin RA, Zakeri Z. 2016. Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation. Cell Death Dis 7:e2127. https://doi.org/10.1038/cddis.2015.409
22. Wang X, Liao Y, Yap PL, Png KJ, Tam JP, Liu DX. 2009. Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells. J Virol 83:12462-12472. https://doi.org/10.1128/JVI.01546-09
23. van Nieuwstadt AP, Zetstra T, Boonstra J. 1989. Infection with porcine respiratory coronavirus does not fully protect pigs against intestinal transmissible gastroenteritis virus. Vet Rec 125:58-60. https://doi.org/ 10.1136/vr.125.3.58
24. Cruz JL, Sola I, Becares M, Alberca B, Plana J, Enjuanes L, Zuniga S. 2011. Coronavirus gene 7 counteracts host defenses and modulates virus virulence. PLoS Pathog 7:e1002090. https://doi.org/10.1371/journal.ppat.1002090
25. Baudoux P, Carrat C, Besnardeau L, Charley B, Laude H. 1998. Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J Virol 72:8636-8643
26. La Bonnardiere C, Laude H. 1981. High interferon titer in newborn pig intestine during experimentally induced viral enteritis. Infect Immun 32:28-31
27. Riffault S, Carrat C, van Reeth K, Pensaert M, Charley B. 2001. Interferonalpha-producing cells are localized in gut-associated lymphoid tissues in transmissible gastroenteritis virus (TGEV) infected piglets. Vet Res 32: 71-79. https://doi.org/10.1051/vetres:2001111
28. Zhou Y, Wu W, Xie L, Wang D, Ke Q, Hou Z, Wu X, Fang Y, Chen H, Xiao S, Fang L. 2017. Cellular RNA helicase DDX1 is involved in transmissible gastroenteritis virus nsp14-induced interferon-beta production. Front Immunol 8:940. https://doi.org/10.3389/fimmu.2017.00940
29. Vallabhapurapu S, Karin M. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27: 693-733. https://doi.org/10.1146/annurev.immunol.021908.132641
30. Jiang HY, Wek SA, McGrath BC, Scheuner D, Kaufman RJ, Cavener DR, Wek RC. 2003. Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol Cell Biol 23:5651-5663. https://doi.org/10.1128/MCB.23.16.5651-5663.2003
31. Jiang HY, Wek RC. 2005. GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation. Biochem J 385:371-380. https://doi.org/10.1042/BJ20041164
32. Weiss SR, Navas-Martin S. 2005. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69:635-664. https://doi.org/10.1128/MMBR.69.4.635-664.2005
33. Liu F, Li G, Wen K, Bui T, Cao D, Zhang Y, Yuan L. 2010. Porcine small intestinal epithelial cell line (IPEC-J2) of rotavirus infection as a new model for the study of innate immune responses to rotaviruses and probiotics. Viral Immunol 23:135-149. https://doi.org/10.1089/vim.2009.0088
34. Geens MM, Niewold TA. 2011. Optimizing culture conditions of a porcine epithelial cell line IPEC-J2 through a histological and physiological characterization. Cytotechnology 63:415-423. https://doi.org/10.1007/s10616-011-9362-9
35. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D. 2002. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92-96. https://doi.org/10.1038/415092a
36. Yu CY, Hsu YW, Liao CL, Lin YL. 2006. Flavivirus infection activates the XBP1 pathway of the unfolded protein response to cope with endoplasmic reticulum stress. J Virol 80:11868-11880. https://doi.org/10.1128/JVI.00879-06
37. Lee AH, Iwakoshi NN, Glimcher LH. 2003. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448-7459. https://doi.org/10.1128/MCB.23.21.7448-7459.2003
38. Haze K, Yoshida H, Yanagi H, Yura T, Mori K. 1999. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 10:3787-3799. https://doi.org/10.1091/mbc.10.11.3787
39. Galindo I, Hernaez B, Munoz-Moreno R, Cuesta-Geijo MA, Dalmau-Mena I, Alonso C. 2012. The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection. Cell Death Dis 3:e341. https://doi.org/10.1038/cddis.2012.81
40. Hassan IH, Zhang MS, Powers LS, Shao JQ, Baltrusaitis J, Rutkowski DT, Legge K, Monick MM. 2012. Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J Biol Chem 287:4679-4689. https://doi.org/10.1074/jbc.M111.284695
41. Nair VP, Anang S, Subramani C, Madhvi A, Bakshi K, Srivastava A, Shalimar Nayak B, Ranjith Kumar CT, Surjit M. 2016. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis e virus. PLoS Pathog 12:e1005521. https://doi.org/10.1371/journal.ppat.1005521
42. Reid SP, Shurtleff AC, Costantino JA, Tritsch SR, Retterer C, Spurgers KB, Bavari S. 2014. HSPA5 is an essential host factor for Ebola virus infection. Antiviral Res 109:171-174. https://doi.org/10.1016/j.antiviral.2014.07.004
43. Su YC, Wu JL, Hong JR. 2011. Betanodavirus up-regulates chaperone GRP78 via ER stress: roles of GRP78 in viral replication and host mitochondria-mediated cell death. Apoptosis 16:272-287. https://doi.org/10.1007/s10495-010-0565-x
44. Prostko CR, Brostrom MA, Malara EM, Brostrom CO. 1992. Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78. J Biol Chem 267:16751-16754
45. Ozcan U, Ozcan L, Yilmaz E, Duvel K, Sahin M, Manning BD, Hotamisligil GS. 2008. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 29:541-551. https://doi.org/10.1016/j.molcel.2007.12.023
46. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS. 2006. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137-1140. https://doi.org/10.1126/science.1128294
47. Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, Silverman RH, Neubert TA, Baxendale IR, Ron D, Harding HP. 2012. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci U S A 109:E869-E878. https://doi.org/10.1073/pnas.1115623109
48. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J. 2005. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307: 935-939. https://doi.org/10.1126/science.1101902
49. Guo L, Yu H, Gu W, Luo X, Li R, Zhang J, Xu Y, Yang L, Shen N, Feng L, Wang Y. 2016. Autophagy negatively regulates transmissible gastroenteritis virus replication. Sci Rep 6:23864. https://doi.org/10.1038/srep23864
50. Yeomans A, Thirdborough SM, Valle-Argos B, Linley A, Krysov S, Hidalgo MS, Leonard E, Ishfaq M, Wagner SD, Willis AE, Steele AJ, Stevenson FK, Forconi F, Coldwell MJ, Packham G. 2016. Engagement of the B-cell receptor of chronic lymphocytic leukemia cells drives global and MYCspecific mRNA translation. Blood 127:449-457. https://doi.org/10.1182/ blood-2015-07-660969
51. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P. 2013. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2:e00498. https://doi.org/10.7554/eLife.00498
52. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. 26 February 2015. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife 4. https://doi.org/10.7554/eLife.05033
53. Zhu L, Yang X, Mou C, Yang Q. 2017. Transmissible gastroenteritis virus does not suppress IFN-beta induction but is sensitive to IFN in IPEC-J2 cells. Vet Microbiol 199:128-134. https://doi.org/10.1016/j.vetmic.2016.12.031
54. Cruz JL, Becares M, Sola I, Oliveros JC, Enjuanes L, Zuniga S. 2013. Alphacoronavirus protein 7 modulates host innate immune response. J Virol 87:9754-9767. https://doi.org/10.1128/JVI.01032-13
55. Becares M, Pascual-Iglesias A, Nogales A, Sola I, Enjuanes L, Zuniga S. 2016. Mutagenesis of coronavirus nsp14 reveals its potential role in modulation of the innate immune response. J Virol 90:5399-5414. https://doi.org/10.1128/JVI.03259-15
56. Ding Z, An K, Xie L, Wu W, Zhang R, Wang D, Fang Y, Chen H, Xiao S, Fang L. 2017. Transmissible gastroenteritis virus infection induces NFkappaB activation through RLR-mediated signaling. Virology 507: 170-178. https://doi.org/10.1016/j.virol.2017.04.024
57. Jordan LT, Derbyshire JB. 1995. Antiviral action of interferon-alpha against porcine transmissible gastroenteritis virus. Vet Microbiol 45: 59-70. https://doi.org/10.1016/0378-1135(94)00118-G
58. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732-738. https://doi.org/10.1038/35099560
59. Minakshi R, Padhan K, Rani M, Khan N, Ahmad F, Jameel S. 2009. The SARS coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One 4:e8342. https://doi.org/10.1371/journal.pone.0008342
60. Favreau DJ, Desforges M, St-Jean JR, Talbot PJ. 2009. A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus. Virology 395:255-267. https://doi.org/10.1016/j.virol.2009.09.026
61. Wang Y, Li JR, Sun MX, Ni B, Huan C, Huang L, Li C, Fan HJ, Ren XF, Mao X. 2014. Triggering unfolded protein response by 2-deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation. Antiviral Res 106: 33-41. https://doi.org/10.1016/j.antiviral.2014.03.007
62. Raaben M, Groot Koerkamp MJ, Rottier PJ, de Haan CA. 2007. Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and pro-transmissible gastroenteritis virus (TGEV) infected piglets. Vet Res 32: 71-79. https://doi.org/10.1051/vetres:2001111
63. Zhou Y, Wu W, Xie L, Wang D, Ke Q, Hou Z, Wu X, Fang Y, Chen H, Xiao S, Fang L. 2017. Cellular RNA helicase DDX1 is involved in transmissible gastroenteritis virus nsp14-induced interferon-beta production. Front Immunol 8:940. https://doi.org/10.3389/fimmu.2017.00940
64. Vallabhapurapu S, Karin M. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27: 693-733. https://doi.org/10.1146/annurev.immunol.021908.132641
65. Jiang HY, Wek SA, McGrath BC, Scheuner D, Kaufman RJ, Cavener DR, Wek RC. 2003. Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol Cell Biol 23:5651-5663. https://doi.org/10.1128/MCB.23.16.5651-5663.2003
66. Jiang HY, Wek RC. 2005. GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation. Biochem J 385:371-380. https://doi.org/10.1042/BJ20041164
67. Weiss SR, Navas-Martin S. 2005. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69:635-664. https://doi.org/10.1128/MMBR.69.4.635-664.2005
68. Liu F, Li G, Wen K, Bui T, Cao D, Zhang Y, Yuan L. 2010. Porcine small intestinal epithelial cell line (IPEC-J2) of rotavirus infection as a new model for the study of innate immune responses to rotaviruses and probiotics. Viral Immunol 23:135-149. https://doi.org/10.1089/vim.2009.0088
69. Geens MM, Niewold TA. 2011. Optimizing culture conditions of a porcine epithelial cell line IPEC-J2 through a histological and physiological characterization. Cytotechnology 63:415-423. https://doi.org/10.1007/s10616-011-9362-9
70. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D. 2002. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92-96. https://doi.org/10.1038/415092a
71. Yu CY, Hsu YW, Liao CL, Lin YL. 2006. Flavivirus infection activates the XBP1 pathway of the unfolded protein response to cope with endoplasmic reticulum stress. J Virol 80:11868-11880. https://doi.org/10.1128/JVI.00879-06
72. Lee AH, Iwakoshi NN, Glimcher LH. 2003. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448-7459. https://doi.org/10.1128/MCB.23.21.7448-7459.2003
73. Haze K, Yoshida H, Yanagi H, Yura T, Mori K. 1999. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 10:3787-3799. https://doi.org/10.1091/mbc.10.11.3787
74. Galindo I, Hernaez B, Munoz-Moreno R, Cuesta-Geijo MA, Dalmau-Mena I, Alonso C. 2012. The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection. Cell Death Dis 3:e341. https://doi.org/10.1038/cddis.2012.81
75. Hassan IH, Zhang MS, Powers LS, Shao JQ, Baltrusaitis J, Rutkowski DT, Legge K, Monick MM. 2012. Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J Biol Chem 287:4679-4689. https://doi.org/10.1074/jbc.M111.284695
76. Nair VP, Anang S, Subramani C, Madhvi A, Bakshi K, Srivastava A, Shalimar Nayak B, Ranjith Kumar CT, Surjit M. 2016. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis e virus. PLoS Pathog 12:e1005521. https://doi.org/10.1371/journal.ppat.1005521
77. Reid SP, Shurtleff AC, Costantino JA, Tritsch SR, Retterer C, Spurgers KB, Bavari S. 2014. HSPA5 is an essential host factor for Ebola virus infection. Antiviral Res 109:171-174. https://doi.org/10.1016/j.antiviral.2014.07.004
78. Su YC, Wu JL, Hong JR. 2011. Betanodavirus up-regulates chaperone GRP78 via ER stress: roles of GRP78 in viral replication and host mitochondria-mediated cell death. Apoptosis 16:272-287. https://doi.org/10.1007/s10495-010-0565-x
79. Prostko CR, Brostrom MA, Malara EM, Brostrom CO. 1992. Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78. J Biol Chem 267:16751-16754
80. Ozcan U, Ozcan L, Yilmaz E, Duvel K, Sahin M, Manning BD, Hotamisligil GS. 2008. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 29:541-551. https://doi.org/10.1016/j.molcel.2007.12.023
81. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS. 2006. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137-1140. https://doi.org/10.1126/science.1128294
82. Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, Silverman RH, Neubert TA, Baxendale IR, Ron D, Harding HP. 2012. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci U S A 109:E869-E878. https://doi.org/10.1073/pnas.1115623109
83. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J. 2005. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307: 935-939. https://doi.org/10.1126/science.1101902
84. Guo L, Yu H, Gu W, Luo X, Li R, Zhang J, Xu Y, Yang L, Shen N, Feng L, Wang Y. 2016. Autophagy negatively regulates transmissible gastroenteritis virus replication. Sci Rep 6:23864. https://doi.org/10.1038/srep23864
85. Yeomans A, Thirdborough SM, Valle-Argos B, Linley A, Krysov S, Hidalgo MS, Leonard E, Ishfaq M, Wagner SD, Willis AE, Steele AJ, Stevenson FK, Forconi F, Coldwell MJ, Packham G. 2016. Engagement of the B-cell receptor of chronic lymphocytic leukemia cells drives global and MYCspecific mRNA translation. Blood 127:449-457. https://doi.org/10.1182/ blood-2015-07-660969
86. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P. 2013. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2:e00498. https://doi.org/10.7554/eLife.00498
87. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. 26 February 2015. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife 4. https://doi.org/10.7554/eLife.05033
88. Zhu L, Yang X, Mou C, Yang Q. 2017. Transmissible gastroenteritis virus does not suppress IFN-beta induction but is sensitive to IFN in IPEC-J2 cells. Vet Microbiol 199:128-134. https://doi.org/10.1016/j.vetmic.2016.12.031
89. Cruz JL, Becares M, Sola I, Oliveros JC, Enjuanes L, Zuniga S. 2013. Alphacoronavirus protein 7 modulates host innate immune response. J Virol 87:9754-9767. https://doi.org/10.1128/JVI.01032-13
90. Becares M, Pascual-Iglesias A, Nogales A, Sola I, Enjuanes L, Zuniga S. 2016. Mutagenesis of coronavirus nsp14 reveals its potential role in modulation of the innate immune response. J Virol 90:5399-5414. https://doi.org/10.1128/JVI.03259-15
91. Ding Z, An K, Xie L, Wu W, Zhang R, Wang D, Fang Y, Chen H, Xiao S, Fang L. 2017. Transmissible gastroenteritis virus infection induces NFkappaB activation through RLR-mediated signaling. Virology 507: 170-178. https://doi.org/10.1016/j.virol.2017.04.024
92. Jordan LT, Derbyshire JB. 1995. Antiviral action of interferon-alpha against porcine transmissible gastroenteritis virus. Vet Microbiol 45: 59-70. https://doi.org/10.1016/0378-1135(94)00118-G
93. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3 Nature 413:732-738. https://doi.org/10.1038/35099560
94. Minakshi R, Padhan K, Rani M, Khan N, Ahmad F, Jameel S. 2009. The SARS coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One 4:e8342. https://doi.org/10.1371/journal.pone.0008342
95. Favreau DJ, Desforges M, St-Jean JR, Talbot PJ. 2009. A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus. Virology 395:255-267. https://doi.org/10.1016/j.virol.2009.09.026
96. Wang Y, Li JR, Sun MX, Ni B, Huan C, Huang L, Li C, Fan HJ, Ren XF, Mao X. 2014. Triggering unfolded protein response by 2-deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation. Antiviral Res 106: 33-41. https://doi.org/10.1016/j.antiviral.2014.03.007
97. Raaben M, Groot Koerkamp MJ, Rottier PJ, de Haan CA. 2007. Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and pro-cessing bodies. Cell Microbiol 9:2218-2229. https://doi.org/10.1111/j.1462-5822.2007.00951.x
98. Narayanan K, Huang C, Lokugamage K, Kamitani W, Ikegami T, Tseng CT, Makino S. 2008. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. J Virol 82:4471-4479. https://doi.org/10.1128/JVI.02472-07
99. Connor JH, Lyles DS. 2005. Inhibition of host and viral translation during vesicular stomatitis virus infection. eIF2 is responsible for the inhibition of viral but not host translation. J Biol Chem 280:13512-13519. https:// doi.org/10.1074/jbc.M501156200
100. Desmet EA, Anguish LJ, Parker JS. 2014. Virus-mediated compartmentalization of the host translational machinery. mBio 5:e01463-14. https:// doi.org/10.1128/mBio.01463-14
101. Zhang C, Guo L, Jia X, Wang T, Wang J, Sun Z, Wang L, Li X, Tan F, Tian K. 2015. Construction of a triple gene-deleted Chinese pseudorabies virus variant and its efficacy study as a vaccine candidate on suckling piglets. Vaccine 33:2432-2437. https://doi.org/10.1016/j.vaccine.2015.03.094