#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Capsid Protein VP4 of Human Rhinovirus Induces Membrane Permeability by the Formation of a Size-Selective Multimeric Pore


Human rhinovirus (HRV) is a non-enveloped virus of the picornavirus family and is responsible for respiratory infections (common colds) costing billions of dollars ($) annually. There remains no vaccine or licensed drug to prevent or reduce infection. Related members of the picornavirus family include significant pathogens such as poliovirus, enterovirus 71 and foot-and-mouth disease virus, for which improved control measures are also required. A fundamental step in virus infection is the delivery of the viral genetic material through the barrier of the cellular membrane. Viruses such as HIV and influenza are enveloped in an outer membrane which can fuse with the host cell membrane to allow the viral genome to penetrate into the cytoplasm. However, non-enveloped viruses such as picornaviruses lack a membrane and the mechanisms for penetration of the membrane by these viruses remain poorly understood. The capsid protein VP4 has previously been implicated in the delivery of the picornavirus genome. In this study we demonstrate that HRV VP4 interacts with membranes to make them permeable by the formation of multimeric, size-selective membrane pores with properties consistent with the transport of viral genome through the membrane. This function of VP4 provides a novel antiviral target for this family of viruses.


Vyšlo v časopise: Capsid Protein VP4 of Human Rhinovirus Induces Membrane Permeability by the Formation of a Size-Selective Multimeric Pore. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004294
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004294

Souhrn

Human rhinovirus (HRV) is a non-enveloped virus of the picornavirus family and is responsible for respiratory infections (common colds) costing billions of dollars ($) annually. There remains no vaccine or licensed drug to prevent or reduce infection. Related members of the picornavirus family include significant pathogens such as poliovirus, enterovirus 71 and foot-and-mouth disease virus, for which improved control measures are also required. A fundamental step in virus infection is the delivery of the viral genetic material through the barrier of the cellular membrane. Viruses such as HIV and influenza are enveloped in an outer membrane which can fuse with the host cell membrane to allow the viral genome to penetrate into the cytoplasm. However, non-enveloped viruses such as picornaviruses lack a membrane and the mechanisms for penetration of the membrane by these viruses remain poorly understood. The capsid protein VP4 has previously been implicated in the delivery of the picornavirus genome. In this study we demonstrate that HRV VP4 interacts with membranes to make them permeable by the formation of multimeric, size-selective membrane pores with properties consistent with the transport of viral genome through the membrane. This function of VP4 provides a novel antiviral target for this family of viruses.


Zdroje

1. PlemperRK (2011) Cell entry of enveloped viruses. Current Opinion in Virology 1: 92–100.

2. HarrisonSC (2008) Viral membrane fusion. Nature Structural & Molecular Biology 15: 690–698.

3. MoyerCL, NemerowGR (2011) Viral weapons of membrane destruction: variable modes of membrane penetration by non-enveloped viruses. Current Opinion in Virology 1: 44–49.

4. Johnson JE (2010) Cell Entry by Non-Enveloped Viruses. In: Johnson JE, editor. Cell Entry by Non-Enveloped Viruses. pp. 1–229.

5. MakelaMJ, PuhakkaT, RuuskanenO, LeinonenM, SaikkuP, et al. (1998) Viruses and bacteria in the etiology of the common cold. Journal of Clinical Microbiology 36: 539–542.

6. GernJE (2010) The ABCs of Rhinoviruses, Wheezing, and Asthma. Journal of Virology 84: 7418–7426.

7. JacksonDJ, JohnstonSL (2010) The role of viruses in acute exacerbations of asthma. Journal of Allergy and Clinical Immunology 125: 1178–1187.

8. ChowM, NewmanJFE, FilmanD, HogleJM, RowlandsDJ, et al. (1987) Myristylation of picornavirus capsid protein VP4 and its structural significance. Nature, UK 237: 482–486.

9. HogleJM (2002) Poliovirus cell entry: Common structural themes in viral cell entry pathways. Annual Review of Microbiology 56: 677–702.

10. TuthillTJ, GroppelliE, HogleJM, RowlandsDJ (2010) Picornaviruses. Curr Top Microbiol Immunol

11. FuchsR, BlaasD (2010) Uncoating of human rhinoviruses. Reviews in Medical Virology 20: 281–297.

12. FricksCE, HogleJM (1990) Cell-induced conformational change in poliovirus - externalization of the amino terminus of vp1 is responsible for liposome binding. Journal of Virology 64: 1934–1945.

13. TuthillTJ, BubeckD, RowlandsDJ, HogleJM (2006) Characterization of early steps in the poliovirus infection process: Receptor-decorated liposomes induce conversion of the virus to membrane-anchored entry-intermediate particles. Journal of Virology 80: 172–180.

14. DanthiP, TostesonM, LiQH, ChowM (2003) Genome delivery and ion channel properties are altered in VP4 mutants of poliovirus. Journal of Virology 77: 5266–5274.

15. MoscufoN, YafalAG, RogoveA, HogleJ, ChowM (1993) A mutation in VP4 defines a new step in the late stages of cell entry by poliovirus. Journal of Virology 67: 5075–5078.

16. StraussM, LevyHC, BostinaM, FilmanDJ, HogleJM (2013) RNA Transfer from Poliovirus 135S Particles across Membranes Is Mediated by Long Umbilical Connectors. Journal of virology 87: 3903–3914.

17. BrabecM, SchoberD, WagnerE, BayerN, MurphyRF, et al. (2005) Opening of size-selective pores in endosomes during human rhinovirus serotype 2 in vivo uncoating monitored by single-organelle flow analysis. Journal of Virology 79: 1008–1016.

18. DavisMP, BottleyG, BealesLP, KillingtonRA, RowlandsDJ, et al. (2008) Recombinant VP4 of human rhinovirus induces permeability in model membranes. Journal of Virology 82: 4169–4174.

19. TostesonMT, WangH, NaumovA, ChowM (2004) Poliovirus binding to its receptor in lipid bilayers results in particle-specific, temperature-sensitive channels. Journal of General Virology 85: 1581–1589.

20. PrchlaE, KuechlerE, BlaasD, FuchsR (1994) Uncoating of human rhinovirus serotype-2 from late endosomes. Journal of Virology 68: 3713–3723.

21. BayerN, PrchlaE, SchwabM, BlaasD, FuchsR (1999) Human rhinovirus HRV14 uncoats from early endosomes in the presence of bafilomycin. Febs Letters 463: 175–178.

22. HuotariJ, HeleniusA (2011) Endosome maturation. Embo Journal 30: 3481–3500.

23. BelloJ, BelloHR, GranadosE (1982) Conformation and aggregation of melittin - dependence on pH and concentration. Biochemistry 21: 461–465.

24. LadokhinAS, SelstedME, WhiteSH (1997) Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: Pore formation by melittin. Biophysical Journal 72: 1762–1766.

25. ParenteRA, NirS, SzokaFC (1990) Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. Biochemistry 29: 8720–8728.

26. NicolF, NirS, SzokaFC (2000) Effect of phospholipid composition on an amphipathic peptide-mediated pore formation in bilayer vesicles. Biophysical Journal 78: 818–829.

27. ParkSC, KimJY, ShinSO, JeongCY, KimMH, et al. (2006) Investigation of toroidal pore and oligomerization by melittin using transmission electron microscopy. Biochemical and Biophysical Research Communications 343: 222–228.

28. TostesonMT, ChowM (1997) Characterization of the ion channels formed by poliovirus in planar lipid membranes. Journal of Virology 71: 507–511.

29. LiQ, YafalAG, LeeYM, HogleJ, ChowM (1994) Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature. J Virol 68: 3965–3970.

30. LewisJK, BothnerB, SmithTJ, SiuzdakG (1998) Antiviral agent blocks breathing of the common cold virus. Proc Natl Acad Sci U S A 95: 6774–6778.

31. ReshMD (1999) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochimica Et Biophysica Acta-Molecular Cell Research 1451: 1–16.

32. YalovskyS, Rodriguez-ConcepcionM, GruissemW (1999) Lipid modifications of proteins - slipping in and out of membranes. Trends in Plant Science 4: 439–445.

33. Martin-BelmonteF, Lopez-GuerreroJA, CarrascoL, AlonsoMA (2000) The amino-terminal nine amino acid sequence of poliovirus capsid VP4 protein is sufficient to confer N-myristoylation and targeting to detergent-insoluble membranes. Biochemistry 39: 1083–1090.

34. XiaoC, TuthillTJ, KellyCMB, ChallinorLJ, ChipmanPR, et al. (2004) Discrimination among rhinovirus serotypes for a variant ICAM-1 receptor molecule. Journal of Virology 78: 10034–10044.

35. HooverlittyH, GreveJM (1993) Formation of rhinovirus-soluble ICAM-1 complexes and conformational-changes in the virion. Journal of Virology 67: 390–397.

36. BilekG, MatschekoNM, Pickl-HerkA, WeissVU, SubiratsX, et al. (2011) Liposomal Nanocontainers as Models for Viral Infection: Monitoring Viral Genomic RNA Transfer through Lipid Membranes. Journal of Virology 85: 8368–8375.

37. BubeckD, FilmanDJ, ChengNQ, StevenAC, HogleJM, et al. (2005) The structure of the poliovirus 135S cell entry intermediate at 10-Angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. Journal of Virology 79: 7745–7755.

38. LinJ, LeeLY, RoivainenM, FilmanDJ, HogleJM, et al. (2012) Structure of the Fab-Labeled “Breathing” State of Native Poliovirus. Journal of Virology 86: 5959–5962.

39. BostinaM, LevyH, FilmanDJ, HogleJM (2011) Poliovirus RNA Is Released from the Capsid near a Twofold Symmetry Axis. Journal of Virology 85: 776–783.

40. WangX, PengW, RenJ, HuZ, XuJ, et al. (2012) A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. Nature Structural & Molecular Biology 19: 424–429.

41. RenJ, WangX, HuZ, GaoQ, SunY, et al. (2013) Picornavirus uncoating intermediate captured in atomic detail. Nature communications 4: 1929–1929.

42. KatpallyU, FuTM, FreedDC, CasimiroDR, SmithTJ (2009) Antibodies to the Buried N Terminus of Rhinovirus VP4 Exhibit Cross-Serotypic Neutralization. Journal of Virology 83: 7040–7048.

43. ClarkeD, GriffinS, BealesL, GelaisCS, BurgessS, et al. (2006) Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. Journal of Biological Chemistry 281: 37057–37068.

44. AndreckaJ, LewisR, BrucknerF, LehmannE, CramerP, et al. (2008) Single-molecule tracking of mRNA exiting from RNA polymerase II. Proc Natl Acad Sci U S A 105: 135–140.

45. KorzhevaN, MustaevA, KozlovM, MalhotraA, NikiforovV, et al. (2000) A structural model of transcription elongation. Science 289: 619–625.

46. AkesonM, BrantonD, KasianowiczJJ, BrandinE, DeamerDW (1999) Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. Biophys J 77: 3227–3233.

47. PohMK, YipA, ZhangS, PriestleJP, MaNL, et al. (2009) A small molecule fusion inhibitor of dengue virus. Antiviral Research 84: 260–266.

48. SchmidtAG, LeeK, YangPL, HarrisonSC (2012) Small-Molecule Inhibitors of Dengue-Virus Entry. Plos Pathogens 8: e1002627 doi:10.1371/journal.ppat.1002627

49. LiuS, WuS, JiangS (2007) HIV entry inhibitors targeting gp41: From polypeptides to small-molecule compounds. Current Pharmaceutical Design 13: 143–162.

50. ZhouG, ChuS (2013) Discovery of Small Molecule Fusion Inhibitors Targeting HIV-1 gp41. Current Pharmaceutical Design 19: 1818–1826.

51. LeeWM, WangWS, RueckertRR (1995) Complete sequence of the RNA genome of human rhinovirus-16, a clinically useful common cold virus belonging to the ICAM-1 receptor group. Virus Genes 9: 177–181.

52. TuthillTJ, HarlosK, WalterTS, KnowlesNJ, GroppelliE, et al. (2009) Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism? PLoS Pathog 5: e1000620.

53. TangG, PengL, BaldwinPR, MannDS, JiangW, et al. (2007) EMAN2: An extensible image processing suite for electron microscopy. Journal of Structural Biology 157: 38–46.

54. HohnM, TangG, GoodyearG, BaldwinPR, HuangZ, et al. (2007) SPARX, a new environment for Cryo-EM image processing. Journal of Structural Biology 157: 47–55.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#