Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation

English version

Autoři: Michèle Brocard ^aff001; Valentina Iadevaia ^aff001; Philipp Klein ^aff002; Belinda Hall ^aff001; Glenys Lewis ^aff001; Jia Lu ^aff003; James Burke ^aff004; Margaret M. Willcocks ^aff001; Roy Parker ^aff004; Ian G. Goodfellow ^aff003; Alessia Ruggieri ^aff002; Nicolas Locker ^aff001
Působiště autorů: Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom ^aff001; Department of Infectious Diseases, Molecular Virology, Centre for Integrative Infectious Disease Research, University of Heidelberg, Heidelberg, Germany ^aff002; Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom ^aff003; Department of Biochemistry, University of Colorado, Boulder, CO, United States of America ^aff004; Howard Hughes Medical Institute, University of Colorado, Boulder, CO, United States of America ^aff005
Vyšlo v časopise: Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation. PLoS Pathog 16(1): e1008250. doi:10.1371/journal.ppat.1008250
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008250

Souhrn

Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Here we examined how norovirus interacts with the eIF2α signaling axis controlling translation and stress granules. While norovirus infection represses host cell translation, our mechanistic analyses revealed that eIF2α signaling mediated by the stress kinase GCN2 is uncoupled from translational stalling. Moreover, infection results in a redistribution of the RNA-binding protein G3BP1 to replication complexes and remodelling of its interacting partners, allowing the avoidance from canonical stress granules. These results define novel strategies by which norovirus undergo efficient replication whilst avoiding the host stress response and manipulating the G3BP1 interactome.

Klíčová slova:

Cellular stress responses – Immunoprecipitation – Interaction networks – Norovirus – Phosphorylation – Protein translation – Viral replication – Calicivirus infection

Zdroje

1. McCormick C, Khaperskyy DA. Translation inhibition and stress granules in the antiviral immune response. Nat Rev Immunol. 2017;17(10):647–60. doi: 10.1038/nri.2017.63 28669985.

2. Piccirillo CA, Bjur E, Topisirovic I, Sonenberg N, Larsson O. Translational control of immune responses: from transcripts to translatomes. Nature immunology. 2014;15(6):503–11. doi: 10.1038/ni.2891 24840981.

3. Walsh D, Mathews MB, Mohr I. Tinkering with translation: protein synthesis in virus-infected cells. Cold Spring Harbor perspectives in biology. 2013;5(1):a012351. Epub 2012/12/05. doi: 10.1101/cshperspect.a012351 23209131.

4. Hoang HD, Graber TE, Alain T. Battling for Ribosomes: Translational Control at the Forefront of the Antiviral Response. J Mol Biol. 2018;430(14):1965–92. doi: 10.1016/j.jmb.2018.04.040 29746850.

5. Lu L, Han AP, Chen JJ. Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses. Mol Cell Biol. 2001;21(23):7971–80. doi: 10.1128/MCB.21.23.7971-7980.2001 11689689; PubMed Central PMCID: PMC99965.

6. Deng J, Harding HP, Raught B, Gingras AC, Berlanga JJ, Scheuner D, et al. Activation of GCN2 in UV-irradiated cells inhibits translation. Curr Biol. 2002;12(15):1279–86. doi: 10.1016/s0960-9822(02)01037-0 12176355.

7. Farrell PJ, Balkow K, Hunt T, Jackson RJ, Trachsel H. Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis. Cell. 1977;11(1):187–200. doi: 10.1016/0092-8674(77)90330-0 559547.

8. Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999;397(6716):271–4. doi: 10.1038/16729 9930704.

9. Garcia MA, Meurs EF, Esteban M. The dsRNA protein kinase PKR: virus and cell control. Biochimie. 2007;89(6–7):799–811. doi: 10.1016/j.biochi.2007.03.001 17451862.

10. Kedersha N, Anderson P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem Soc Trans. 2002;30(Pt 6):963–9. doi: 10.1042/bst0300963 12440955.

11. Protter DS, Parker R. Principles and Properties of Stress Granules. Trends Cell Biol. 2016. doi: 10.1016/j.tcb.2016.05.004 27289443.

12. Van Treeck B, Protter DSW, Matheny T, Khong A, Link CD, Parker R. RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome. Proc Natl Acad Sci U S A. 2018;115(11):2734–9. doi: 10.1073/pnas.1800038115 29483269; PubMed Central PMCID: PMC5856561.

13. Maharana S, Wang J, Papadopoulos DK, Richter D, Pozniakovsky A, Poser I, et al. RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science. 2018;360(6391):918–21. doi: 10.1126/science.aar7366 29650702; PubMed Central PMCID: PMC6091854.

14. Youn JY, Dunham WH, Hong SJ, Knight JDR, Bashkurov M, Chen GI, et al. High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Mol Cell. 2018;69(3):517–32 e11. doi: 10.1016/j.molcel.2017.12.020 29395067.

15. Jain S, Wheeler JR, Walters RW, Agrawal A, Barsic A, Parker R. ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell. 2016;164(3):487–98. doi: 10.1016/j.cell.2015.12.038 26777405; PubMed Central PMCID: PMC4733397.

16. Aulas A, Fay MM, Lyons SM, Achorn CA, Kedersha N, Anderson P, et al. Stress-specific differences in assembly and composition of stress granules and related foci. J Cell Sci. 2017;130(5):927–37. doi: 10.1242/jcs.199240 28096475; PubMed Central PMCID: PMC5358336.

17. Khong A, Matheny T, Jain S, Mitchell SF, Wheeler JR, Parker R. The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules. Mol Cell. 2017;68(4):808–20 e5. doi: 10.1016/j.molcel.2017.10.015 29129640; PubMed Central PMCID: PMC5728175.

18. Namkoong S, Ho A, Woo YM, Kwak H, Lee JH. Systematic Characterization of Stress-Induced RNA Granulation. Mol Cell. 2018;70(1):175–87 e8. doi: 10.1016/j.molcel.2018.02.025 29576526.

19. Reineke LC, Kedersha N, Langereis MA, van Kuppeveld FJ, Lloyd RE. Stress granules regulate double-stranded RNA-dependent protein kinase activation through a complex containing G3BP1 and Caprin1. MBio. 2015;6(2):e02486. doi: 10.1128/mBio.02486-14 25784705; PubMed Central PMCID: PMC4453520.

20. Poblete-Duran N, Prades-Perez Y, Vera-Otarola J, Soto-Rifo R, Valiente-Echeverria F. Who Regulates Whom? An Overview of RNA Granules and Viral Infections. Viruses. 2016;8(7). doi: 10.3390/v8070180 27367717; PubMed Central PMCID: PMC4974515.

21. Reineke LC, Lloyd RE. Diversion of stress granules and P-bodies during viral infection. Virology. 2013;436(2):255–67. doi: 10.1016/j.virol.2012.11.017 23290869; PubMed Central PMCID: PMC3611887.

22. Lopman BA, Trivedi T, Vicuna Y, Costantini V, Collins N, Gregoricus N, et al. Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status. J Infect Dis. 2015;211(11):1813–21. doi: 10.1093/infdis/jiu672 25505295; PubMed Central PMCID: PMC4425937.

23. Karst SM. Pathogenesis of noroviruses, emerging RNA viruses. Viruses. 2010;2(3):748–81. doi: 10.3390/v2030748 21994656; PubMed Central PMCID: PMC3185648.

24. Bartsch SM, Lopman BA, Ozawa S, Hall AJ, Lee BY. Global Economic Burden of Norovirus Gastroenteritis. PLoS One. 2016;11(4):e0151219. doi: 10.1371/journal.pone.0151219 27115736; PubMed Central PMCID: PMC4846012.

25. Pringle K, Lopman B, Vega E, Vinje J, Parashar UD, Hall AJ. Noroviruses: epidemiology, immunity and prospects for prevention. Future Microbiol. 2015;10(1):53–67. doi: 10.2217/fmb.14.102 25598337.

26. Capizzi T, Makari-Judson G, Steingart R, Mertens WC. Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases. BMC infectious diseases. 2011;11:131. Epub 2011/05/19. doi: 10.1186/1471-2334-11-131 21586142; PubMed Central PMCID: PMC3118142.

27. Schwartz S, Vergoulidou M, Schreier E, Loddenkemper C, Reinwald M, Schmidt-Hieber M, et al. Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood. 2011;117(22):5850–6. Epub 2011/04/14. doi: 10.1182/blood-2010-12-325886 21487110.

28. Desselberger U, Goodfellow I. Noroviruses: a global cause of acute gastroenteritis. The Lancet Infectious diseases. 2014;14(8):664–5. doi: 10.1016/S1473-3099(14)70776-5 24981040.

29. Stuart RL, Tan K, Mahar JE, Kirkwood CD, Andrew Ramsden C, Andrianopoulos N, et al. An outbreak of necrotizing enterocolitis associated with norovirus genotype GII.3. The Pediatric infectious disease journal. 2010;29(7):644–7. Epub 2010/07/01. doi: 10.1097/inf.0b013e3181d824e1 20589982.

30. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell. 2010;141(7):1135–45. Epub 2010/07/07. doi: 10.1016/j.cell.2010.05.009 20602997; PubMed Central PMCID: PMC2908380.

31. Bartnicki E, Cunha JB, Kolawole AO, Wobus CE. Recent advances in understanding noroviruses. F1000Res. 2017;6:79. doi: 10.12688/f1000research.10081.1 28163914; PubMed Central PMCID: PMC5270584.

32. Zhang D, Tan M, Zhong W, Xia M, Huang P, Jiang X. Human intestinal organoids express histo-blood group antigens, bind norovirus VLPs, and support limited norovirus replication. Sci Rep. 2017;7(1):12621. doi: 10.1038/s41598-017-12736-2 28974702; PubMed Central PMCID: PMC5626734.

33. Oka T, Stoltzfus GT, Zhu C, Jung K, Wang Q, Saif LJ. Attempts to grow human noroviruses, a sapovirus, and a bovine norovirus in vitro. PLoS One. 2018;13(2):e0178157. doi: 10.1371/journal.pone.0178157 29438433; PubMed Central PMCID: PMC5810978.

34. Karst SM, Wobus CE, Lay M, Davidson J, Virgin HWt. STAT1-dependent innate immunity to a Norwalk-like virus. Science. 2003;299(5612):1575–8. doi: 10.1126/science.1077905 12624267.

35. Wobus CE, Thackray LB, Virgin HWt. Murine norovirus: a model system to study norovirus biology and pathogenesis. J Virol. 2006;80(11):5104–12. doi: 10.1128/JVI.02346-05 16698991; PubMed Central PMCID: PMC1472167.

36. Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, et al. Discovery of a proteinaceous cellular receptor for a norovirus. Science. 2016;353(6302):933–6. doi: 10.1126/science.aaf1220 27540007; PubMed Central PMCID: PMC5484048.

37. Royall E, Locker N. Translational Control during Calicivirus Infection. Viruses. 2016;8(4):104. doi: 10.3390/v8040104 27104553; PubMed Central PMCID: PMC4848598.

38. Olspert A, Hosmillo M, Chaudhry Y, Peil L, Truve E, Goodfellow I. Protein-RNA linkage and posttranslational modifications of feline calicivirus and murine norovirus VPg proteins. PeerJ. 2016;4:e2134. doi: 10.7717/peerj.2134 27375966; PubMed Central PMCID: PMC4928471.

39. Emmott E, Sweeney TR, Goodfellow I. A Cell-based Fluorescence Resonance Energy Transfer (FRET) Sensor Reveals Inter- and Intragenogroup Variations in Norovirus Protease Activity and Polyprotein Cleavage. J Biol Chem. 2015;290(46):27841–53. doi: 10.1074/jbc.M115.688234 26363064; PubMed Central PMCID: PMC4646915.

40. Emmott E, Sorgeloos F, Caddy SL, Vashist S, Sosnovtsev S, Lloyd R, et al. Norovirus-Mediated Modification of the Translational Landscape via Virus and Host-Induced Cleavage of Translation Initiation Factors. Mol Cell Proteomics. 2017;16(4 suppl 1):S215-S29. doi: 10.1074/mcp.M116.062448 28087593; PubMed Central PMCID: PMC5393397.

41. Humoud MN, Doyle N, Royall E, Willcocks MM, Sorgeloos F, van Kuppeveld F, et al. Feline Calicivirus infection disrupts the assembly of cytoplasmic stress granules and induces G3BP1 cleavage. J Virol. 2016. doi: 10.1128/JVI.00647-16 27147742.

42. Nathans D. Puromycin Inhibition of Protein Synthesis: Incorporation of Puromycin into Peptide Chains. Proc Natl Acad Sci U S A. 1964;51:585–92. doi: 10.1073/pnas.51.4.585 14166766; PubMed Central PMCID: PMC300121.

43. David A, Dolan BP, Hickman HD, Knowlton JJ, Clavarino G, Pierre P, et al. Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol. 2012;197(1):45–57. doi: 10.1083/jcb.201112145 22472439; PubMed Central PMCID: PMC3317795.

44. Obrig TG, Culp WJ, McKeehan WL, Hardesty B. The mechanism by which cycloheximide and related glutarimide antibiotics inhibit peptide synthesis on reticulocyte ribosomes. J Biol Chem. 1971;246(1):174–81. 5541758.

45. Royall E, Doyle N, Abdul-Wahab A, Emmott E, Morley SJ, Goodfellow I, et al. Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection. J Biol Chem. 2015;290(8):4748–58. doi: 10.1074/jbc.M114.602649 25561727; PubMed Central PMCID: PMC4335213.

46. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife. 2015;4. doi: 10.7554/eLife.05033 25719440; PubMed Central PMCID: PMC4341466.

47. Zyryanova AF, Weis F, Faille A, Alard AA, Crespillo-Casado A, Sekine Y, et al. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science. 2018;359(6383):1533–6. doi: 10.1126/science.aar5129 29599245; PubMed Central PMCID: PMC5889100.

48. Lee AS. Mammalian stress response: induction of the glucose-regulated protein family. Curr Opin Cell Biol. 1992;4(2):267–73. doi: 10.1016/0955-0674(92)90042-b 1599691.

49. Jiang HY, Wek SA, McGrath BC, Scheuner D, Kaufman RJ, Cavener DR, et al. 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. 2003;23(16):5651–63. doi: 10.1128/MCB.23.16.5651-5663.2003 12897138; PubMed Central PMCID: PMC166326.

50. Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T. Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics. 2006;5(4):749–57. doi: 10.1074/mcp.T500024-MCP200 16340016.

51. Kinoshita-Kikuta E, Kinoshita E, Yamada A, Endo M, Koike T. Enrichment of phosphorylated proteins from cell lysate using a novel phosphate-affinity chromatography at physiological pH. Proteomics. 2006;6(19):5088–95. doi: 10.1002/pmic.200600252 16941569.

52. Rabouw HH, Langereis MA, Anand AA, Visser LJ, de Groot RJ, Walter P, et al. Small molecule ISRIB suppresses the integrated stress response within a defined window of activation. Proc Natl Acad Sci U S A. 2019;116(6):2097–102. doi: 10.1073/pnas.1815767116 30674674; PubMed Central PMCID: PMC6369741.

53. Knutsen JH, Rodland GE, Boe CA, Haland TW, Sunnerhagen P, Grallert B, et al. Stress-induced inhibition of translation independently of eIF2alpha phosphorylation. J Cell Sci. 2015;128(23):4420–7. doi: 10.1242/jcs.176545 26493332; PubMed Central PMCID: PMC4712817.

54. Ishimura R, Nagy G, Dotu I, Chuang JH, Ackerman SL. Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation. Elife. 2016;5. doi: 10.7554/eLife.14295 27085088; PubMed Central PMCID: PMC4917338.

55. Brazeau JF, Rosse G. Triazolo[4,5-d]pyrimidine Derivatives as Inhibitors of GCN2. ACS Med Chem Lett. 2014;5(4):282–3. doi: 10.1021/ml500052f 24900825; PubMed Central PMCID: PMC4027772.

56. Hyde JL, Sosnovtsev SV, Green KY, Wobus C, Virgin HW, Mackenzie JM. Mouse norovirus replication is associated with virus-induced vesicle clusters originating from membranes derived from the secretory pathway. J Virol. 2009;83(19):9709–19. doi: 10.1128/JVI.00600-09 19587041; PubMed Central PMCID: PMC2748037.

57. Hyde JL, Gillespie LK, Mackenzie JM. Mouse norovirus 1 utilizes the cytoskeleton network to establish localization of the replication complex proximal to the microtubule organizing center. J Virol. 2012;86(8):4110–22. doi: 10.1128/JVI.05784-11 22301146; PubMed Central PMCID: PMC3318650.

58. Doerflinger SY, Cortese M, Romero-Brey I, Menne Z, Tubiana T, Schenk C, et al. Membrane alterations induced by nonstructural proteins of human norovirus. PLoS Pathog. 2017;13(10):e1006705. doi: 10.1371/journal.ppat.1006705 29077760; PubMed Central PMCID: PMC5678787.

59. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, et al. Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol. 2000;151(6):1257–68. doi: 10.1083/jcb.151.6.1257 11121440; PubMed Central PMCID: PMC2190599.

60. Kedersha N, Panas MD, Achorn CA, Lyons S, Tisdale S, Hickman T, et al. G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits. J Cell Biol. 2016;212(7):845–60. doi: 10.1083/jcb.201508028 27022092; PubMed Central PMCID: PMC4810302.

61. Markmiller S, Soltanieh S, Server KL, Mak R, Jin W, Fang MY, et al. Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules. Cell. 2018;172(3):590–604 e13. doi: 10.1016/j.cell.2017.12.032 29373831; PubMed Central PMCID: PMC5969999.

62. Tsai WC, Gayatri S, Reineke LC, Sbardella G, Bedford MT, Lloyd RE. Arginine Demethylation of G3BP1 Promotes Stress Granule Assembly. J Biol Chem. 2016;291(43):22671–85. doi: 10.1074/jbc.M116.739573 27601476; PubMed Central PMCID: PMC5077203.

63. Panas MD, Kedersha N, Schulte T, Branca RM, Ivanov P, Anderson P. Phosphorylation of G3BP1-S149 does not influence stress granule assembly. J Cell Biol. 2019;218(7):2425–32. doi: 10.1083/jcb.201801214 31171631; PubMed Central PMCID: PMC6605800.

64. Matsuki H, Takahashi M, Higuchi M, Makokha GN, Oie M, Fujii M. Both G3BP1 and G3BP2 contribute to stress granule formation. Genes Cells. 2013;18(2):135–46. doi: 10.1111/gtc.12023 23279204.

65. Han TW, Kato M, Xie S, Wu LC, Mirzaei H, Pei J, et al. Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell. 2012;149(4):768–79. doi: 10.1016/j.cell.2012.04.016 22579282.

66. Panas MD, Kedersha N, McInerney GM. Methods for the characterization of stress granules in virus infected cells. Methods. 2015;90:57–64. doi: 10.1016/j.ymeth.2015.04.009 25896634.

67. Wheeler JR, Matheny T, Jain S, Abrisch R, Parker R. Distinct stages in stress granule assembly and disassembly. Elife. 2016;5. doi: 10.7554/eLife.18413 27602576; PubMed Central PMCID: PMC5014549.

68. Niewidok B, Igaev M, Pereira da Graca A, Strassner A, Lenzen C, Richter CP, et al. Single-molecule imaging reveals dynamic biphasic partition of RNA-binding proteins in stress granules. J Cell Biol. 2018;217(4):1303–18. doi: 10.1083/jcb.201709007 29463567; PubMed Central PMCID: PMC5881506.

69. Chaudhry Y, Nayak A, Bordeleau ME, Tanaka J, Pelletier J, Belsham GJ, et al. Caliciviruses differ in their functional requirements for eIF4F components. J Biol Chem. 2006;281(35):25315–25. doi: 10.1074/jbc.M602230200 16835235.

70. Bordeleau ME, Mori A, Oberer M, Lindqvist L, Chard LS, Higa T, et al. Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. Nat Chem Biol. 2006;2(4):213–20. doi: 10.1038/nchembio776 16532013.

71. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, et al. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol. 2005;169(6):871–84. doi: 10.1083/jcb.200502088 15967811; PubMed Central PMCID: PMC2171635.

72. Wheeler JR, Jain S, Khong A, Parker R. Isolation of yeast and mammalian stress granule cores. Methods. 2017;126:12–7. doi: 10.1016/j.ymeth.2017.04.020 28457979.

73. Haga Y, Kanda T, Nakamoto S, Nakamura M, Sasaki R, Wu S, et al. Interferon induces interleukin 8 and bone marrow stromal cell antigen 2 expression, inhibiting the production of hepatitis B virus surface antigen from human hepatocytes. Biochemical and biophysical research communications. 2017;486(3):858–63. doi: 10.1016/j.bbrc.2017.03.150 28363866.

74. Shivanna V, Kim Y, Chang KO. Ceramide formation mediated by acid sphingomyelinase facilitates endosomal escape of caliciviruses. Virology. 2015;483:218–28. doi: 10.1016/j.virol.2015.04.022 25985440; PubMed Central PMCID: PMC4516657.

75. Gadea G, Blangy A. Dock-family exchange factors in cell migration and disease. Eur J Cell Biol. 2014;93(10–12):466–77. doi: 10.1016/j.ejcb.2014.06.003 25022758.

76. Shulman Z, Pasvolsky R, Woolf E, Grabovsky V, Feigelson SW, Erez N, et al. DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration. Blood. 2006;108(7):2150–8. doi: 10.1182/blood-2006-04-017608 16772603.

77. Panas MD, Schulte T, Thaa B, Sandalova T, Kedersha N, Achour A, et al. Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation. PLoS Pathog. 2015;11(2):e1004659. doi: 10.1371/journal.ppat.1004659 25658430; PubMed Central PMCID: PMC4450067.

78. Anderson P, Kedersha N. Stressful initiations. J Cell Sci. 2002;115(Pt 16):3227–34. 12140254.

79. Roth H, Magg V, Uch F, Mutz P, Klein P, Haneke K, et al. Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses. MBio. 2017;8(1). doi: 10.1128/mBio.02150-16 28074025; PubMed Central PMCID: PMC5225315.

80. Song Y, Mugavero J, Stauft CB, Wimmer E. Dengue and Zika Virus 5' Untranslated Regions Harbor Internal Ribosomal Entry Site Functions. MBio. 2019;10(2). doi: 10.1128/mBio.00459-19 30967466; PubMed Central PMCID: PMC6456755.

81. Berlanga JJ, Ventoso I, Harding HP, Deng J, Ron D, Sonenberg N, et al. Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA viruses. EMBO J. 2006;25(8):1730–40. doi: 10.1038/sj.emboj.7601073 16601681; PubMed Central PMCID: PMC1440839.

82. Fritzlar S, Aktepe TE, Chao YW, Kenney ND, McAllaster MR, Wilen CB, et al. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2alpha Axis. MBio. 2019;10(3). doi: 10.1128/mBio.00960-19 31213553; PubMed Central PMCID: PMC6581855.

83. Witteveldt J, Blundell R, Maarleveld JJ, McFadden N, Evans DJ, Simmonds P. The influence of viral RNA secondary structure on interactions with innate host cell defences. Nucleic Acids Res. 2014;42(5):3314–29. doi: 10.1093/nar/gkt1291 24335283; PubMed Central PMCID: PMC3950689.

84. Pham AM, Santa Maria FG, Lahiri T, Friedman E, Marie IJ, Levy DE. PKR Transduces MDA5-Dependent Signals for Type I IFN Induction. PLoS Pathog. 2016;12(3):e1005489. doi: 10.1371/journal.ppat.1005489 26939124; PubMed Central PMCID: PMC4777437.

85. McCartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin HW, Colonna M. MDA-5 recognition of a murine norovirus. PLoS Pathog. 2008;4(7):e1000108. doi: 10.1371/journal.ppat.1000108 18636103; PubMed Central PMCID: PMC2443291.

86. McFadden N, Bailey D, Carrara G, Benson A, Chaudhry Y, Shortland A, et al. Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4. PLoS Pathog. 2011;7(12):e1002413. doi: 10.1371/journal.ppat.1002413 22174679; PubMed Central PMCID: PMC3234229.

87. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19(6):727–40. doi: 10.1016/j.molcel.2005.08.014 16153868.

88. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122(5):669–82. doi: 10.1016/j.cell.2005.08.012 16125763.

89. Hosmillo M, Lu J, McAllaster MR, Eaglesham JB, Wang X, Emmott E, et al. Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation. Elife. 2019;8. doi: 10.7554/eLife.46681 31403400; PubMed Central PMCID: PMC6739877.

90. Hubstenberger A, Courel M, Benard M, Souquere S, Ernoult-Lange M, Chouaib R, et al. P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. Mol Cell. 2017;68(1):144–57 e5. doi: 10.1016/j.molcel.2017.09.003 28965817.

91. Thorne L, Lu J, Chaudhry Y, Goodfellow I. miR-155 induction is a marker of murine norovirus infection but does not contribute to control of replication in vivo. Wellcome Open Res. 2018;3:42. doi: 10.12688/wellcomeopenres.14188.1 29900416; PubMed Central PMCID: PMC5974592.

92. Ruggieri A, Dazert E, Metz P, Hofmann S, Bergeest JP, Mazur J, et al. Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe. 2012;12(1):71–85. doi: 10.1016/j.chom.2012.05.013 22817989; PubMed Central PMCID: PMC3873964.

93. Pizzato M, Erlwein O, Bonsall D, Kaye S, Muir D, McClure MO. A one-step SYBR Green I-based product-enhanced reverse transcriptase assay for the quantitation of retroviruses in cell culture supernatants. J Virol Methods. 2009;156(1–2):1–7. doi: 10.1016/j.jviromet.2008.10.012 19022294.

94. McCune BT, Tang W, Lu J, Eaglesham JB, Thorne L, Mayer AE, et al. Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2. MBio. 2017;8(4). doi: 10.1128/mBio.00668-17 28698274; PubMed Central PMCID: PMC5513711.

95. Vizcaino JA, Csordas A, del-Toro N, Dianes JA, Griss J, Lavidas I, et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44(D1):D447–56. doi: 10.1093/nar/gkv1145 26527722; PubMed Central PMCID: PMC4702828.