Electron Tomography Reveals the Steps in Filovirus Budding

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The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses.

Vyšlo v časopise: Electron Tomography Reveals the Steps in Filovirus Budding. PLoS Pathog 6(4): e32767. doi:10.1371/journal.ppat.1000875
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000875

Souhrn

Zdroje

1. PetersCJ

2005 Marburg and Ebola–arming ourselves against the deadly filoviruses. N Engl J Med 352 2571 2573

2. FeldmannH

JonesS

KlenkHD

SchnittlerHJ

2003 Ebola virus: from discovery to vaccine. Nat Rev Immunol 3 677 685

3. HoenenT

GrosethA

FalzaranoD

FeldmannH

2006 Ebola virus: unravelling pathogenesis to combat a deadly disease. Trends Mol Med 12 206 215

4. BauschDG

BorchertM

GreinT

RothC

SwanepoelR

2003 Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo. Emerg Infect Dis 9 1531 1537

5. BorchertM

Muyembe-TamfumJJ

ColebundersR

LibandeM

SabueM

2002 Short communication: a cluster of Marburg virus disease involving an infant. Trop Med Int Health 7 902 906

6. CDC CfDCaP 2005 Outbreak of Marburg virus hemorrhagic fever–Angola, October 1, 2004-March 29, 2005. Morbidity and Mortality Weekly Report 308 309

7. ColebundersR

SleursH

PirardP

BorchertM

LibandeM

2004 Organisation of health care during an outbreak of Marburg haemorrhagic fever in the Democratic Republic of Congo, 1999. J Infect 48 347 353

8. LigonBL

2005 Outbreak of Marburg hemorrhagic fever in Angola: a review of the history of the disease and its biological aspects. Semin Pediatr Infect Dis 16 219 224

9. BukreyevAA

VolchkovVE

BlinovVM

DrygaSA

NetesovSV

1995 The complete nucleotide sequence of the Popp (1967) strain of Marburg virus: a comparison with the Musoke (1980) strain. Arch Virol 140 1589 1600

10. FeldmannH

MuhlbergerE

RandolfA

WillC

KileyMP

1992 Marburg virus, a filovirus: messenger RNAs, gene order, and regulatory elements of the replication cycle. Virus Res 24 1 19

11. SanchezA

KileyMP

KlenkHD

FeldmannH

1992 Sequence analysis of the Marburg virus nucleoprotein gene: comparison to Ebola virus and other non-segmented negative-strand RNA viruses. J Gen Virol 73 (Pt2) 347 357

12. MavrakisM

KolesnikovaL

SchoehnG

BeckerS

RuigrokRW

2002 Morphology of Marburg virus NP-RNA. Virology 296 300 307

13. BeckerS

RinneC

HofsassU

KlenkHD

MühlbergerE

1998 Interactions of Marburg virus nucleocapsid proteins. Virology 249 406 417

14. BeckerS

SpiessM

KlenkHD

1995 The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol 76 393 399

15. MarziA

GrambergT

SimmonsG

MollerP

RennekampAJ

2004 DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus. J Virol 78 12090 12095

16. BambergS

KolesnikovaL

MollerP

KlenkHD

BeckerS

2005 VP24 of Marburg virus influences formation of infectious particles. J Virol 79 13421 13433

17. KolesnikovaL

BambergS

BerghöferB

BeckerS

2004 The matrix protein of Marburg virus is transported to the plasma membrane along cellular membranes: exploiting the retrograde late endosomal pathway. J Virol 78 2383 2393

18. KolesnikovaL

BeckerS

2004 Virus Maturation.

KlenkH-D

FeldmannH

Ebola and Marburg Viruses: Molecular and Cellular Biology: Horizon Scientific Press

19. GeisbertTW

JaaxNK

1998 Marburg hemorrhagic fever: report of a case studied by immunohistochemistry and electron microscopy. Ultrastruct Pathol 22 3 17

20. GeisbertTW

JahrlingPB

1995 Differentiation of filoviruses by electron microscopy. Virus Res 39 129 150

21. KolesnikovaL

BuganyH

KlenkHD

BeckerS

2002 VP40, the matrix protein of Marburg virus, is associated with membranes of the late endosomal compartment. J Virol 76 1825 1838

22. KolesnikovaL

MühlbergerE

RyabchikovaE

BeckerS

2000 Ultrastructural organization of recombinant Marburg virus nucleoprotein: comparison with Marburg virus inclusions. J Virol 74 3899 3904

23. KolesnikovaL

BohilAB

CheneyRE

BeckerS

2007 Budding of Marburgvirus is associated with filopodia. Cell Microbiol 9 939 951

24. PetersD

MüllerG

SlenczkaWG

1971 Morphology, development, and classification of the Marburg virus.

Martini GAaSR

Springer-Verlag, Berlin 68 83

25. AtilganE

SunSX

2007 Shape transitions in lipid membranes and protein mediated vesicle fusion and fission. J Chem Phys 126 095102

26. FalangaA

CantisaniM

PedoneC

GaldieroS

2009 Membrane fusion and fission: enveloped viruses. Protein Pept Lett 16 751 759

27. WelschS

MullerB

KrausslichHG

2007 More than one door - Budding of enveloped viruses through cellular membranes. FEBS Lett 581 2089 2097

28. ChenBJ

LambRA

2008 Mechanisms for enveloped virus budding: can some viruses do without an ESCRT? Virology 372 221 232

29. BieniaszPD

2009 The cell biology of HIV-1 virion genesis. Cell Host Microbe 5 550 558

30. KolesnikovaL

RyabchikovaE

ShestopalovA

BeckerS

2007 Basolateral Budding of Marburg Virus: VP40 Retargets Viral Glycoprotein GP to the Basolateral Surface. J Infect Dis 196 S232 S236

31. WirblichC

TanGS

PapaneriA

GodlewskiPJ

OrensteinJM

2008 PPEY motif within the rabies virus (RV) matrix protein is essential for efficient virion release and RV pathogenicity. J Virol 82 9730 9738

32. CompansRW

DimmockNJ

1969 An electron microscopic study of single-cycle infection of chick embryo fibroblasts by influenza virus. Virology 39 499 515

33. NodaT

SagaraH

YenA

TakadaA

KidaH

2006 Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature 439 490 492

34. RobertsPC

CompansRW

1998 Host cell dependence of viral morphology. Proc Natl Acad Sci U S A 95 5746 5751

35. OrensteinJ

SheltonE

LazzariniRA

1975 Association of ribosomes with intracellular vesicular stomatitis virus particles. J Virol 16 447 452

36. NodaT

EbiharaH

MuramotoY

FujiiK

TakadaA

2006 Assembly and budding of Ebolavirus. PLoS Pathog 2 e99 doi:10.1371/journal.ppat.0020099

37. SosinskyGE

CrumJ

JonesYZ

LanmanJ

SmarrB

2008 The combination of chemical fixation procedures with high pressure freezing and freeze substitution preserves highly labile tissue ultrastructure for electron tomography applications. J Struct Biol 161 359 371

38. McIntoshJR

AntonyC

DubochetJ

DutcherSK

GiddingsTH

2007 Cellular Electron Microscopy;

McIntoshJR

London Academic Press

39. EllisDS

StamfordS

LloydG

BowenET

PlattGS

1979 Ebola and Marburg viruses: I. Some ultrastructural differences between strains when grown in Vero cells. J Med Virol 4 201 211

40. FabrikantG

LataS

RichesJD

BriggsJA

WeissenhornW

2009 Computational Model of Membrane Fission Catalyzed by ESCRT-III. PLoS Comput Biol 5 e1000575 doi:10.1371/journal.pcbi.1000575

41. OrensteinJ

JohnsonL

SheltonE

LazzariniRA

1976 The shape of vesicular stomatitis virus. Virology 71 291 301

42. GeP

TsaoJ

ScheinS

GreenTJ

LuoM

2010 Cryo-EM Model of the Bullet-Shaped Vesicular Stomatitis Virus. Science 327 689 693

43. OdenwaldWF

ArnheiterH

Dubois-DalcqM

LazzariniRA

1986 Stereo images of vesicular stomatitis virus assembly. J Virol 57 922 932

44. BourmakinaSV

Garcia-SastreA

2003 Reverse genetics studies on the filamentous morphology of influenza A virus. J Gen Virol 84 517 527

45. MurakiY

MurataT

TakashitaE

MatsuzakiY

SugawaraK

2007 A mutation on influenza C virus M1 protein affects virion morphology by altering the membrane affinity of the protein. J Virol 81 8766 8773

46. RobertsPC

LambRA

CompansRW

1998 The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation. Virology 240 127 137

47. TimenA

KoopmansMP

VossenAC

van DoornumGJ

GuntherS

2009 Response to imported case of Marburg hemorrhagic fever, the Netherland. Emerg Infect Dis 15 1171 1175

48. FunkeC

BeckerS

DartschH

KlenkHD

MuhlbergerE

1995 Acylation of the Marburg virus glycoprotein. Virology 208 289 297

49. HierholzerJC

KillingtonRA

1996 Virus isolation and quantitation.

MahyBW

KangroHO

London, United Kingdom Academic Press Limited

50. MillerS

KastnerS

Krijnse-LockerJ

BuhlerS

BartenschlagerR

2007 The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem 282 8873 8882

51. GriffithsG

SimonsK

WarrenG

TokuyasuKT

1983 Immunoelectron microscopy using thin, frozen sections: application to studies of the intracellular transport of Semliki Forest virus spike glycoproteins. Methods Enzymol 96 466 485

52. GriffithsG

1993 Chapter 11 Quantitative Aspects of Immunocytochemistry. Fine Structure Immunocytochemistry Berlin Springer Verlag

53. HoogJL

SchwartzC

NoonAT

O'TooleET

MastronardeDN

2007 Organization of interphase microtubules in fission yeast analyzed by electron tomography. Dev Cell 12 349 361

54. KremerJR

MastronardeDN

McIntoshJR

1996 Computer visualization of three-dimensional image data using IMOD. J Struct Biol 116 71 76