An Interaction between Glutathione and the Capsid Is Required for the Morphogenesis of C-Cluster Enteroviruses
Enteroviruses are plus stranded RNA viruses in the Picornaviridae family that cause as many as 3 billion infections per year. Enterovirus morphogenesis, which involves the encapsidation of newly made viral RNAs, has been studied for many years but the process is still poorly understood. Elucidation of this process is important for the development of drug treatments for a variety of human diseases. We describe the role of glutathione, an important cellular reducing agent, in enterovirus morphogenesis by studying the inhibition of GSH biosynthesis with BSO on viral proliferation. We discovered that GSH directly interacts with viral capsid precursors and the mature virus. In the presence of BSO the accumulation of a small capsid precusor (pentamer) is reduced and consequently no mature viruses are produced in virus-infected cells. Drug resistant viruses are easily isolated with mutations located in two of the capsid proteins, VP1 and VP3. We propose a model to explain the role of GSH in enterovirus morphogenesis, which is to stabilize the capsid precursors and the mature virus during and after the encapsidation of the progeny viral RNA by direct interaction with capsid proteins.
Vyšlo v časopise:
An Interaction between Glutathione and the Capsid Is Required for the Morphogenesis of C-Cluster Enteroviruses. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004052
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004052
Souhrn
Enteroviruses are plus stranded RNA viruses in the Picornaviridae family that cause as many as 3 billion infections per year. Enterovirus morphogenesis, which involves the encapsidation of newly made viral RNAs, has been studied for many years but the process is still poorly understood. Elucidation of this process is important for the development of drug treatments for a variety of human diseases. We describe the role of glutathione, an important cellular reducing agent, in enterovirus morphogenesis by studying the inhibition of GSH biosynthesis with BSO on viral proliferation. We discovered that GSH directly interacts with viral capsid precursors and the mature virus. In the presence of BSO the accumulation of a small capsid precusor (pentamer) is reduced and consequently no mature viruses are produced in virus-infected cells. Drug resistant viruses are easily isolated with mutations located in two of the capsid proteins, VP1 and VP3. We propose a model to explain the role of GSH in enterovirus morphogenesis, which is to stabilize the capsid precursors and the mature virus during and after the encapsidation of the progeny viral RNA by direct interaction with capsid proteins.
Zdroje
1. PompellaA, PaolicchiA, CortiA, FranziniM (2013) Gamma-glutamyltransferase, H2O2-induced apoptosis and expression of catalase. Toxicol In Vitro 27: 991.
2. GriffithOW, MeisterA (1979) Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem 254: 7558–7560.
3. SmithAD, DawsonH (2006) Glutathione is required for efficient production of infectious picornavirus virions. Virology 353: 258–267.
4. GaraciE, PalamaraAT, CirioloMR, D'AgostiniC, Abdel-LatifMS, et al. (1997) Intracellular GSH content and HIV replication in human macrophages. J Leukoc Biol 62: 54–59.
5. CaiJ, ChenY, SethS, FurukawaS, CompansRW, et al. (2003) Inhibition of influenza infection by glutathione. Free Radic Biol Med 34: 928–936.
6. PalamaraAT, PernoCF, CirioloMR, DiniL, BalestraE, et al. (1995) Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res 27: 237–253.
7. MacchiaI, PalamaraAT, BueC, SaviniP, CirioloM, et al. (1999) Increased replication of Sendai virus in morphine-treated epithelial cells: evidence for the involvement of the intracellular levels of glutathione. Int J Immunopharmacol 21: 185–193.
8. FenwickML, CooperPD (1962) Early interactions between poliovirus and ERK cells: some observations on the nature and significance of the rejected particles. Virology 18: 212–223.
9. MikamiT, SatohN, HatayamaI, NakaneA (2004) Buthionine sulfoximine inhibits cytopathic effect and apoptosis induced by infection with human echovirus 9. Arch Virol 149: 1117–1128.
10. Lonberg-HolmK, GosserLB, KauerJC (1975) Early alteration of poliovirus in infected cells and its specific inhibition. J Gen Virol 27: 329–342.
11. McSharryJJ, CaliguiriLA, EggersHJ (1979) Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. Virology 97: 307–315.
12. GellerR, VignuzziM, AndinoR, FrydmanJ (2007) Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes Dev 21: 195–205.
13. Ypma-WongMF, DewaltPG, JohnsonVH, LambJG, SemlerBL (1988) Protein 3CD is the major poliovirus proteinase responsible for cleavage of the P1 capsid precursor. Virology 166: 265–270.
14. VerlindenY, CuconatiA, WimmerE, RombautB (2000) Cell-free synthesis of poliovirus: 14S subunits are the key intermediates in the encapsidation of poliovirus RNA. J Gen Virol 81: 2751–2754.
15. PfisterT, EggerD, BienzK (1995) Poliovirus subviral particles associated with progeny RNA in the replication complex. J Gen Virol 76(Pt 1): 63–71.
16. NugentCI, KirkegaardK (1995) RNA binding properties of poliovirus subviral particles. J Virol 69: 13–22.
17. BoeyeA, RombautB (1992) The proteins of poliovirus. Prog Med Virol 39: 139–166.
18. WimmerE, HellenCU, CaoX (1993) Genetics of poliovirus. Annu Rev Genet 27: 353–436.
19. Rueckert RR (1996) Picornaviridae: the viruses and their replication.; B.N. Fields DMKaPMH, editor. Philadelphia: Philadelphia: Lippincott-Raven.
20. LiC, WangJC, TaylorMW, ZlotnickA (2012) In vitro assembly of an empty picornavirus capsid follows a dodecahedral path. J Virol 86: 13062–13069.
21. LiuY, WangC, MuellerS, PaulAV, WimmerE, et al. (2010) Direct interaction between two viral proteins, the nonstructural protein 2C and the capsid protein VP3, is required for enterovirus morphogenesis. PLoS Pathog 6: e1001066.
22. WangC, JiangP, SandC, PaulAV, WimmerE (2012) Alanine scanning of poliovirus 2CATPase reveals new genetic evidence that capsid protein/2CATPase interactions are essential for morphogenesis. J Virol 86: 9964–9975.
23. KewOM, SutterRW, de GourvilleEM, DowdleWR, PallanschMA (2005) Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol 59: 587–635.
24. NomotoA, OmataT, ToyodaH, KugeS, HorieH, et al. (1982) Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc Natl Acad Sci U S A 79: 5793–5797.
25. HogleJM, ChowM, FilmanDJ (1985) Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229: 1358–1365.
26. ButanC, FilmanDJ, HogleJM (2014) Cryo-Electron Microscopy Reconstruction Shows Poliovirus 135S Particles Poised for Membrane Interaction and RNA Release. J Virol 88: 1758–1770.
27. PfisterT, WimmerE (1999) Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J Biol Chem 274: 6992–7001.
28. PutnakJR, PhillipsBA (1981) Picornaviral structure and assembly. Microbiol Rev 45: 287–315.
29. TianY, JiangW, GaoN, ZhangJ, ChenW, et al. (2010) Inhibitory effects of glutathione on dengue virus production. Biochem Biophys Res Commun 397: 420–424.
30. MacadamAJ, FergusonG, ArnoldC, MinorPD (1991) An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain. J Virol 65: 5225–5231.
31. PutnakJR, PhillipsBA (1981) Differences between poliovirus empty capsids formed in vivo and those formed in vitro: a role for the morphopoietic factor. J Virol 40: 173–183.
32. PhillipsBA, WiemertS (1978) In vitro assembly of poliovirus. V. Evidence that the self-assembly activity of 14 S particles is independent of extract assembly factor(s) and host proteins. Virology 88: 92–104.
33. AnsardiDC, PorterDC, MorrowCD (1992) Myristylation of poliovirus capsid precursor P1 is required for assembly of subviral particles. J Virol 66: 4556–4563.
34. MarcD, MassonG, GirardM, van der WerfS (1990) Lack of myristoylation of poliovirus capsid polypeptide VP0 prevents the formation of virions or results in the assembly of noninfectious virus particles. J Virol 64: 4099–4107.
35. MoscufoN, SimonsJ, ChowM (1991) Myristoylation is important at multiple stages in poliovirus assembly. J Virol 65: 2372–2380.
36. BreindlM (1971) The structure of heated poliovirus particles. J Gen Virol 11: 147–156.
37. LevyHC, BostinaM, FilmanDJ, HogleJM (2010) Catching a virus in the act of RNA release: a novel poliovirus uncoating intermediate characterized by cryo-electron microscopy. J Virol 84: 4426–4441.
38. BelnapDM, McDermottBMJr, FilmanDJ, ChengN, TrusBL, et al. (2000) Three-dimensional structure of poliovirus receptor bound to poliovirus. Proc Natl Acad Sci U S A 97: 73–78.
39. van der WerfS, BradleyJ, WimmerE, StudierFW, DunnJJ (1986) Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc Natl Acad Sci U S A 83: 2330–2334.
40. JiangP, FaaseJA, ToyodaH, PaulA, WimmerE, et al. (2007) Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication. Proc Natl Acad Sci U S A 104: 9457–9462.
41. MollaA, PaulAV, WimmerE (1991) Cell-free, de novo synthesis of poliovirus. Science 254: 1647–1651.
42. ChenZ, ChumakovK, DragunskyE, KouiavskaiaD, MakiyaM, et al. (2011) Chimpanzee-human monoclonal antibodies for treatment of chronic poliovirus excretors and emergency postexposure prophylaxis. J Virol 85: 4354–4362.
43. PettersenEF, GoddardTD, HuangCC, CouchGS, GreenblattDM, et al. (2004) UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem 25: 1605–1612.
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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