Co-opted Oxysterol-Binding ORP and VAP Proteins Channel Sterols to RNA Virus Replication Sites via Membrane Contact Sites

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Viruses recruit cellular membranes and subvert cellular proteins involved in lipid biosynthesis to build viral replicase complexes and replication organelles. Among the lipids, sterols are important components of membranes, affecting the shape and curvature of membranes. In this paper, the tombusvirus replication protein is shown to co-opt cellular Oxysterol-binding protein related proteins (ORPs), whose deletion in yeast model host leads to decreased tombusvirus replication. In addition, tombusviruses also subvert Scs2p VAP protein to facilitate the formation of membrane contact sites (MCSs), where membranes are juxtaposed, likely channeling lipids to the replication sites. In all, these events result in redistribution and enrichment of sterols at the sites of viral replication in yeast and plant cells. Using in vitro viral replication assay with artificial vesicles, we show stimulation of tombusvirus replication by sterols. Thus, co-opting cellular ORP and VAP proteins to form MCSs serves the virus need to generate abundant sterol-rich membrane surfaces for tombusvirus replication.

Vyšlo v časopise: Co-opted Oxysterol-Binding ORP and VAP Proteins Channel Sterols to RNA Virus Replication Sites via Membrane Contact Sites. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004388
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004388

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Zdroje

1. NagyPD (2008) Yeast as a model host to explore plant virus-host interactions. Annu Rev Phytopathol 46: 217–242.

2. HuangYW, HuCC, LinNS, HsuYH (2012) Unusual roles of host metabolic enzymes and housekeeping proteins in plant virus replication. Curr Opin Virol 2: 676–682.

3. ShullaA, RandallG (2012) Hepatitis C virus-host interactions, replication, and viral assembly. Curr Opin Virol 2: 725–732.

4. MineA, OkunoT (2012) Composition of plant virus RNA replicase complexes. Curr Opin Virol 2: 669–675.

5. BelovGA, van KuppeveldFJ (2012) (+)RNA viruses rewire cellular pathways to build replication organelles. Curr Opin Virol 2: 740–747.

6. NagyPD, PoganyJ (2012) The dependence of viral RNA replication on co-opted host factors. Nature Reviews Microbiology 10: 137–149.

7. PanavasT, ServieneE, BrasherJ, NagyPD (2005) Yeast genome-wide screen reveals dissimilar sets of host genes affecting replication of RNA viruses. Proc Natl Acad Sci U S A 102: 7326–7331.

8. CherryS, DoukasT, ArmknechtS, WhelanS, WangH, et al. (2005) Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition. Genes Dev 19: 445–452.

9. JiangY, ServieneE, GalJ, PanavasT, NagyPD (2006) Identification of essential host factors affecting tombusvirus RNA replication based on the yeast Tet promoters Hughes Collection. J Virol 80: 7394–7404.

10. KushnerDB, LindenbachBD, GrdzelishviliVZ, NoueiryAO, PaulSM, et al. (2003) Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci U S A 100: 15764–15769.

11. KrishnanMN, NgA, SukumaranB, GilfoyFD, UchilPD, et al. (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455 doi:10.1038/nature07207

12. BarajasD, JiangY, NagyPD (2009) A unique role for the host ESCRT proteins in replication of Tomato bushy stunt virus. PLoS Pathog 5: e1000705.

13. DiazA, WangX, AhlquistP (2010) Membrane-shaping host reticulon proteins play crucial roles in viral RNA replication compartment formation and function. Proc Natl Acad Sci U S A 107: 16291–16296.

14. NeuvonenM, KazlauskasA, MartikainenM, HinkkanenA, AholaT, et al. (2011) SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication. PLoS Pathog 7: e1002383.

15. BarajasD, MartinIF, PoganyJ, RiscoC, NagyPD (2014) Noncanonical Role for the Host Vps4 AAA+ ATPase ESCRT Protein in the Formation of Tomato Bushy Stunt Virus Replicase. PLoS Pathog 10: e1004087.

16. de CastroIF, VolonteL, RiscoC (2013) Virus factories: biogenesis and structural design. Cell Microbiol 15: 24–34.

17. SchaeferEA, ChungRT (2013) HCV and host lipids: an intimate connection. Semin Liver Dis 33: 358–368.

18. den BoonJA, DiazA, AhlquistP (2010) Cytoplasmic viral replication complexes. Cell Host Microbe 8: 77–85.

19. PaulD, BartenschlagerR (2013) Architecture and biogenesis of plus-strand RNA virus replication factories. World J Virol 2: 32–48.

20. NagyPD, PoganyJ (2006) Yeast as a model host to dissect functions of viral and host factors in tombusvirus replication. Virology 344: 211–220.

21. PanavasT, NagyPD (2003) Yeast as a model host to study replication and recombination of defective interfering RNA of Tomato bushy stunt virus. Virology 314: 315–325.

22. NagyPD, PoganyJ, LinJY (2014) How yeast can be used as a genetic platform to explore virus-host interactions: from ‘omics’ to functional studies. Trends Microbiol 22: 309–16 doi: 10.1016/j.tim.2014.02.003

23. PohMK, ShuiG, XieX, ShiPY, WenkMR, et al. (2012) U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication. Antiviral Res 93: 191–198.

24. HwangYT, McCartneyAW, GiddaSK, MullenRT (2008) Localization of the Carnation Italian ringspot virus replication protein p36 to the mitochondrial outer membrane is mediated by an internal targeting signal and the TOM complex. BMC Cell Biol 9: 54.

25. Weber-LotfiF, DietrichA, RussoM, RubinoL (2002) Mitochondrial targeting and membrane anchoring of a viral replicase in plant and yeast cells. J Virol 76: 10485–10496.

26. PoganyJ, StorkJ, LiZ, NagyPD (2008) In vitro assembly of the Tomato bushy stunt virus replicase requires the host Heat shock protein 70. Proc Natl Acad Sci U S A 105: 19956–19961.

27. Shah Nawaz-Ul-RehmanM, Reddisiva PrasanthK, BakerJ, NagyPD (2013) Yeast screens for host factors in positive-strand RNA virus replication based on a library of temperature-sensitive mutants. Methods 59: 207–216.

28. ServieneE, ShapkaN, ChengCP, PanavasT, PhuangratB, et al. (2005) Genome-wide screen identifies host genes affecting viral RNA recombination. Proc Natl Acad Sci U S A 102: 10545–10550.

29. ServieneE, JiangY, ChengCP, BakerJ, NagyPD (2006) Screening of the yeast yTHC collection identifies essential host factors affecting tombusvirus RNA recombination. J Virol 80: 1231–1241.

30. Shah Nawaz-Ul-RehmanM, Martinez-OchoaN, PascalH, SasvariZ, HerbstC, et al. (2012) Proteome-wide overexpression of host proteins for identification of factors affecting tombusvirus RNA replication: an inhibitory role of protein kinase C. J Virol 86: 9384–9395.

31. NagyPD (2011) The roles of host factors in tombusvirus RNA recombination. Adv Virus Res 81: 63–84.

32. NagyPD, PoganyJ (2010) Global genomics and proteomics approaches to identify host factors as targets to induce resistance against Tomato bushy stunt virus. Adv Virus Res 76: 123–177.

33. MenduV, ChiuM, BarajasD, LiZ, NagyPD (2010) Cpr1 cyclophilin and Ess1 parvulin prolyl isomerases interact with the tombusvirus replication protein and inhibit viral replication in yeast model host. Virology 406: 342–351.

34. LiZ, PoganyJ, PanavasT, XuK, EspositoAM, et al. (2009) Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor. Virology 385: 245–260.

35. LiZ, BarajasD, PanavasT, HerbstDA, NagyPD (2008) Cdc34p Ubiquitin-Conjugating Enzyme Is a Component of the Tombusvirus Replicase Complex and Ubiquitinates p33 Replication Protein. J Virol 82: 6911–6926.

36. ServaS, NagyPD (2006) Proteomics analysis of the tombusvirus replicase: Hsp70 molecular chaperone is associated with the replicase and enhances viral RNA replication. J Virol 80: 2162–2169.

37. LiZ, NagyPD (2011) Diverse roles of host RNA binding proteins in RNA virus replication. RNA Biol 8: 305–315.

38. LiZ, PoganyJ, TupmanS, EspositoAM, KinzyTG, et al. (2010) Translation elongation factor 1A facilitates the assembly of the tombusvirus replicase and stimulates minus-strand synthesis. PLoS Pathog 6: e1001175.

39. WangRY, StorkJ, NagyPD (2009) A key role for heat shock protein 70 in the localization and insertion of tombusvirus replication proteins to intracellular membranes. J Virol 83: 3276–3287.

40. JonczykM, PathakKB, SharmaM, NagyPD (2007) Exploiting alternative subcellular location for replication: tombusvirus replication switches to the endoplasmic reticulum in the absence of peroxisomes. Virology 362: 320–330.

41. PanavasT, HawkinsCM, PanavieneZ, NagyPD (2005) The role of the p33:p33/p92 interaction domain in RNA replication and intracellular localization of p33 and p92 proteins of Cucumber necrosis tombusvirus. Virology 338: 81–95.

42. NagyPD, BarajasD, PoganyJ (2012) Host factors with regulatory roles in tombusvirus replication. Curr Opin Virol 2: 685–692.

43. McCartneyAW, GreenwoodJS, FabianMR, WhiteKA, MullenRT (2005) Localization of the tomato bushy stunt virus replication protein p33 reveals a peroxisome-to-endoplasmic reticulum sorting pathway. Plant Cell 17: 3513–3531.

44. KovalevN, NagyPD (2014) The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication. PLoS Pathog 10: e1004051.

45. NagyPD, PoganyJ, LinJY (2014) How yeast can be used as a genetic platform to explore virus-host interactions: from ‘omics’ to functional studies. Trends Microbiol 22: 309–316.

46. SharmaM, SasvariZ, NagyPD (2011) Inhibition of phospholipid biosynthesis decreases the activity of the tombusvirus replicase and alters the subcellular localization of replication proteins. Virology 415: 141–152.

47. SharmaM, SasvariZ, NagyPD (2010) Inhibition of sterol biosynthesis reduces tombusvirus replication in yeast and plants. J Virol 84: 2270–2281.

48. BlochK (1992) Sterol molecule: structure, biosynthesis, and function. Steroids 57: 378–383.

49. BlochKE (1983) Sterol structure and membrane function. CRC Crit Rev Biochem 14: 47–92.

50. SchekmanR (2007) How sterols regulate protein sorting and traffic. Proc Natl Acad Sci U S A 104: 6496–6497.

51. RocheY, Gerbeau-PissotP, BuhotB, ThomasD, BonneauL, et al. (2008) Depletion of phytosterols from the plant plasma membrane provides evidence for disruption of lipid rafts. Faseb J 22: 3980–3991.

52. SchulzTA, ChoiMG, RaychaudhuriS, MearsJA, GhirlandoR, et al. (2009) Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues. J Cell Biol 187: 889–903.

53. RaychaudhuriS, PrinzWA (2010) The diverse functions of oxysterol-binding proteins. Annu Rev Cell Dev Biol 26: 157–177.

54. Weber-BoyvatM, ZhongW, YanD, OlkkonenVM (2013) Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism. Biochem Pharmacol 86: 89–95.

55. RidgwayND (2010) Oxysterol-binding proteins. Subcell Biochem 51: 159–182.

56. SaravananRS, SlabaughE, SinghVR, LapidusLJ, HaasT, et al. (2009) The targeting of the oxysterol-binding protein ORP3a to the endoplasmic reticulum relies on the plant VAP33 homolog PVA12. Plant J 58: 817–830.

57. MesminB, BigayJ, Moser von FilseckJ, Lacas-GervaisS, DrinG, et al. (2013) A Four-Step Cycle Driven by PI(4)P Hydrolysis Directs Sterol/PI(4)P Exchange by the ER-Golgi Tether OSBP. Cell 155: 830–843.

58. StefanCJ, ManfordAG, BairdD, Yamada-HanffJ, MaoY, et al. (2011) Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites. Cell 144: 389–401.

59. LevS, Ben HalevyD, PerettiD, DahanN (2008) The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol 18: 282–290.

60. UmateP (2011) Oxysterol binding proteins (OSBPs) and their encoding genes in Arabidopsis and rice. Steroids 76: 524–529.

61. BehCT, CoolL, PhillipsJ, RineJ (2001) Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157: 1117–1140.

62. PoganyJ, NagyPD (2008) Authentic replication and recombination of Tomato bushy stunt virus RNA in a cell-free extract from yeast. J Virol 82: 5967–5980.

63. BehCT, McMasterCR, KozminskiKG, MenonAK (2012) A detour for yeast oxysterol binding proteins. J Biol Chem 287: 11481–11488.

64. VillasmilML, BankaitisVA, MousleyCJ (2012) The oxysterol-binding protein superfamily: new concepts and old proteins. Biochem Soc Trans 40: 469–473.

65. TakahashiS, YeoY, GreenhagenBT, McMullinT, SongL, et al. (2007) Metabolic engineering of sesquiterpene metabolism in yeast. Biotechnol Bioeng 97: 170–181.

66. CaretteJE, VerverJ, MartensJ, van KampenT, WellinkJ, et al. (2002) Characterization of plant proteins that interact with cowpea mosaic virus ‘60K’ protein in the yeast two-hybrid system. J Gen Virol 83: 885–893.

67. PetersenNH, JoensenJ, McKinneyLV, BrodersenP, PetersenM, et al. (2009) Identification of proteins interacting with Arabidopsis ACD11. J Plant Physiol 166: 661–666.

68. RiscoC, Sanmartin-ConesaE, TzengWP, FreyTK, SeyboldV, et al. (2012) Specific, sensitive, high-resolution detection of protein molecules in eukaryotic cells using metal-tagging transmission electron microscopy. Structure 20: 759–766.

69. DiestraE, FontanaJ, GuichardP, MarcoS, RiscoC (2009) Visualization of proteins in intact cells with a clonable tag for electron microscopy. J Struct Biol 165: 157–168.

70. MillerS, Krijnse-LockerJ (2008) Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol 6: 363–374.

71. HeatonNS, RandallG (2010) Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe 8: 422–432.

72. HsuNY, IlnytskaO, BelovG, SantianaM, ChenYH, et al. (2010) Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell 141: 799–811.

73. ReissS, RebhanI, BackesP, Romero-BreyI, ErfleH, et al. (2011) Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell Host Microbe 9: 32–45.

74. IlnytskaO, SantianaM, HsuNY, DuWL, ChenYH, et al. (2013) Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication. Cell Host Microbe 14: 281–293.

75. NohturfftA, ZhangSC (2009) Coordination of lipid metabolism in membrane biogenesis. Annu Rev Cell Dev Biol 25: 539–566.

76. KrishnanMN, NgA, SukumaranB, GilfoyFD, UchilPD, et al. (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455: 242–245.

77. LiQ, BrassAL, NgA, HuZ, XavierRJ, et al. (2009) A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc Natl Acad Sci U S A 106: 16410–16415.

78. ChangKO (2009) Role of cholesterol pathways in norovirus replication. J Virol 83: 8587–8595.

79. RothwellC, LebretonA, Young NgC, LimJY, LiuW, et al. (2009) Cholesterol biosynthesis modulation regulates dengue viral replication. Virology 389: 8–19.

80. SaganSM, RouleauY, LeggiadroC, SupekovaL, SchultzPG, et al. (2006) The influence of cholesterol and lipid metabolism on host cell structure and hepatitis C virus replication. Biochem Cell Biol 84: 67–79.

81. KapadiaSB, ChisariFV (2005) Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A 102: 2561–2566.

82. AizakiH, LeeKJ, SungVM, IshikoH, LaiMM (2004) Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts. Virology 324: 450–461.

83. MackenzieJM, KhromykhAA, PartonRG (2007) Cholesterol manipulation by West Nile virus perturbs the cellular immune response. Cell Host Microbe 2: 229–239.

84. LeeCJ, LinHR, LiaoCL, LinYL (2008) Cholesterol effectively blocks entry of flavivirus. J Virol 82: 6470–6480.

85. MarquardtMT, PhalenT, KielianM (1993) Cholesterol is required in the exit pathway of Semliki Forest virus. J Cell Biol 123: 57–65.

86. SimonM, JohanssonC, MirazimiA (2009) Crimean-Congo hemorrhagic fever virus entry and replication is clathrin-, pH- and cholesterol-dependent. J Gen Virol 90: 210–215.

87. Amini-Bavil-OlyaeeS, ChoiYJ, LeeJH, ShiM, HuangIC, et al. (2013) The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 13: 452–464.

88. PoganyJ, PanavasT, ServieneE, Nawaz-Ul-RehmanMS, NagyPD (2010) A high-throughput approach for studying virus replication in yeast. Current Protocols in Microbiology 19: 16J.11.11–16J.11.15.

89. PanavasT, ServieneE, PoganyJ, NagyPD (2008) Genome-wide screens for identification of host factors in viral replication. Methods Mol Biol 451: 615–624.

90. RajendranKS, NagyPD (2003) Characterization of the RNA-binding domains in the replicase proteins of tomato bushy stunt virus. J Virol 77: 9244–9258.

91. PanavieneZ, PanavasT, ServaS, NagyPD (2004) Purification of the cucumber necrosis virus replicase from yeast cells: role of coexpressed viral RNA in stimulation of replicase activity. J Virol 78: 8254–8263.

92. BarajasD, LiZ, NagyPD (2009) The Nedd4-type Rsp5p ubiquitin ligase inhibits tombusvirus replication by regulating degradation of the p92 replication protein and decreasing the activity of the tombusvirus replicase. J Virol 83: 11751–11764.

93. PathakKB, SasvariZ, NagyPD (2008) The host Pex19p plays a role in peroxisomal localization of tombusvirus replication proteins. Virology 379: 294–305.

94. WangRY, NagyPD (2008) Tomato bushy stunt virus co-opts the RNA-binding function of a host metabolic enzyme for viral genomic RNA synthesis. Cell Host Microbe 3: 178–187.

95. BehCT, RineJ (2004) A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution. J Cell Sci 117: 2983–2996.

96. XuK, HuangTS, NagyPD (2012) Authentic in vitro replication of two tombusviruses in isolated mitochondrial and endoplasmic reticulum membranes. J Virol 86: 12779–12794.

97. FontanaJ, Lopez-MonteroN, ElliottRM, FernandezJJ, RiscoC (2008) The unique architecture of Bunyamwera virus factories around the Golgi complex. Cell Microbiol 10: 2012–2028.

98. FontanaJ, TzengWP, CalderitaG, Fraile-RamosA, FreyTK, et al. (2007) Novel replication complex architecture in rubella replicon-transfected cells. Cell Microbiol 9: 875–890.

99. RiscoC, RodriguezJR, Lopez-IglesiasC, CarrascosaJL, EstebanM, et al. (2002) Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly. J Virol 76: 1839–1855.

100. KovalevN, PoganyJ, NagyPD (2012) A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis. PLoS Pathog 8: e1002537.