The Ebola Virus Ribonucleoprotein Complex: a Novel VP30-L Interaction Identified

Overview

Journal Virus Res

Specialty Microbiology

Date 2008 Dec 2

PMID 19041915

Citations 53

Authors

A Groseth

J E Charton

M Sauerborn

F Feldmann

S M Jones

T Hoenen

H Feldmann

Affiliations

Soon will be listed here.

Abstract

The ribonucleoprotein (RNP) complex of Ebola virus (EBOV) is known to be a multiprotein/RNA structure, however, knowledge is rather limited regarding the actual protein-protein interactions involved in its formation. Here we show that singularly expressed VP35 and VP30 are present throughout the cytoplasm, while NP forms prominent cytoplasmic inclusions and L forms smaller perinuclear inclusions. We could demonstrate the existence of NP-VP35, NP-VP30 and VP35-L interactions, similar to those described for Marburg virus (MARV) based on the redistribution of protein partners into NP and L inclusion bodies. Significantly, a novel VP30-L interaction was also identified and found to form as part of an NP-VP30-L bridge structure, similar to that formed by VP35. The identification of these interactions allows a preliminary model of the EBOV RNP complex structure to be proposed, and may provide insight into filovirus transcriptional regulation.

Citing Articles

Structural basis for Ebola virus nucleocapsid assembly and function regulated by VP24.

Fujita-Fujiharu Y, Hu S, Hirabayashi A, Takamatsu Y, Ng Y, Houri K Nat Commun. 2025; 16(1):2171.

PMID: 40064872 PMC: 11894184. DOI: 10.1038/s41467-025-57236-4.

Antisense Therapy for Infectious Diseases.

Buthelezi L, Pillay S, Ntuli N, Gcanga L, Guler R Cells. 2023; 12(16).

PMID: 37626929 PMC: 10453568. DOI: 10.3390/cells12162119.

Ebola virus inclusion bodies are liquid organelles whose formation is facilitated by nucleoprotein oligomerization.

Bodmer B, Vallbracht M, Ushakov D, Wendt L, Chlanda P, Hoenen T Emerg Microbes Infect. 2023; 12(2):2223727.

PMID: 37306660 PMC: 10288931. DOI: 10.1080/22221751.2023.2223727.

Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology.

Groseth A, Gardner D, Meade-White K, Amler S, Ebihara H PLoS Negl Trop Dis. 2023; 17(5):e0011355.

PMID: 37235549 PMC: 10218742. DOI: 10.1371/journal.pntd.0011355.

Inhibiting the transcription and replication of Ebola viruses by disrupting the nucleoprotein and VP30 protein interaction with small molecules.

Ma Y, Hong X, Wu F, Xu X, Li R, Zhong J Acta Pharmacol Sin. 2023; 44(7):1487-1499.

PMID: 36759643 PMC: 9909651. DOI: 10.1038/s41401-023-01055-0.

References

Theriault S, Groseth A, Neumann G, Kawaoka Y, Feldmann H . Rescue of Ebola virus from cDNA using heterologous support proteins. Virus Res. 2004; 106(1):43-50. DOI: 10.1016/j.virusres.2004.06.002. View

Moller P, Pariente N, Klenk H, Becker S . Homo-oligomerization of Marburgvirus VP35 is essential for its function in replication and transcription. J Virol. 2005; 79(23):14876-86. PMC: 1287548. DOI: 10.1128/JVI.79.23.14876-14886.2005. View

Modrof J, Muhlberger E, Klenk H, Becker S . Phosphorylation of VP30 impairs ebola virus transcription. J Biol Chem. 2002; 277(36):33099-104. DOI: 10.1074/jbc.M203775200. View

Towner J, Sealy T, Khristova M, Albarino C, Conlan S, Reeder S . Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog. 2008; 4(11):e1000212. PMC: 2581435. DOI: 10.1371/journal.ppat.1000212. View

Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991; 108(2):193-9. DOI: 10.1016/0378-1119(91)90434-d. View

Watanabe S, Noda T, Kawaoka Y . Functional mapping of the nucleoprotein of Ebola virus. J Virol. 2006; 80(8):3743-51. PMC: 1440433. DOI: 10.1128/JVI.80.8.3743-3751.2006. View

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

Huang Y, Xu L, Sun Y, Nabel G . The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell. 2002; 10(2):307-16. DOI: 10.1016/s1097-2765(02)00588-9. View

Muhlberger E, Lotfering B, Klenk H, Becker S . Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes. J Virol. 1998; 72(11):8756-64. PMC: 110291. DOI: 10.1128/JVI.72.11.8756-8764.1998. View

10.

Enterlein S, Volchkov V, Weik M, Kolesnikova L, Volchkova V, Klenk H . Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid protein VP30. J Virol. 2005; 80(2):1038-43. PMC: 1346851. DOI: 10.1128/JVI.80.2.1038-1043.2006. View

11.

Weik M, Modrof J, Klenk H, Becker S, Muhlberger E . Ebola virus VP30-mediated transcription is regulated by RNA secondary structure formation. J Virol. 2002; 76(17):8532-9. PMC: 136988. DOI: 10.1128/jvi.76.17.8532-8539.2002. View

12.

Becker S, Rinne C, Hofsass U, Klenk H, Muhlberger E . Interactions of Marburg virus nucleocapsid proteins. Virology. 1998; 249(2):406-17. DOI: 10.1006/viro.1998.9328. View

13.

Reid S, Cardenas W, Basler C . Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein. Virology. 2005; 341(2):179-89. PMC: 3955989. DOI: 10.1016/j.virol.2005.06.044. View

14.

Duprex W, Collins F, Rima B . Modulating the function of the measles virus RNA-dependent RNA polymerase by insertion of green fluorescent protein into the open reading frame. J Virol. 2002; 76(14):7322-8. PMC: 136336. DOI: 10.1128/jvi.76.14.7322-7328.2002. View

15.

ELLIOTT L, Kiley M, McCormick J . Descriptive analysis of Ebola virus proteins. Virology. 1985; 147(1):169-76. DOI: 10.1016/0042-6822(85)90236-3. View

16.

Sanger C, Muhlberger E, Klenk H, Becker S . Adverse effects of MVA-T7 on the transport of Marburg virus glycoprotein. J Virol Methods. 2001; 91(1):29-35. DOI: 10.1016/s0166-0934(00)00239-1. View

17.

Muhlberger E, Weik M, Volchkov V, Klenk H, Becker S . Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol. 1999; 73(3):2333-42. PMC: 104478. DOI: 10.1128/JVI.73.3.2333-2342.1999. View

18.

Groseth A, Feldmann H, Theriault S, Mehmetoglu G, Flick R . RNA polymerase I-driven minigenome system for Ebola viruses. J Virol. 2005; 79(7):4425-33. PMC: 1061559. DOI: 10.1128/JVI.79.7.4425-4433.2005. View

19.

Hartlieb B, Muziol T, Weissenhorn W, Becker S . Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association. Proc Natl Acad Sci U S A. 2007; 104(2):624-9. PMC: 2111399. DOI: 10.1073/pnas.0606730104. View

20.

Boehmann Y, Enterlein S, Randolf A, Muhlberger E . A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire. Virology. 2005; 332(1):406-17. DOI: 10.1016/j.virol.2004.11.018. View