An assembly model of Rift Valley fever virus

Mirabela Rusu, Richard Bonneau, Michael R. Holbrook, Stanley Watowich, Stefan Birmanns, Willy Wriggers, Alexander Freiberg

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV) is a bunyavirus endemic to Africa and the Arabian Peninsula that infects humans and livestock.The virus encodes two glycoproteins, Gn and Gc, which represent the major structural antigens and are responsible for host cell receptor bind-ing and fusion. Both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. Currently, no experimental three-dimensional structure for any entire bunyavirus glycoprotein is available. Using fold recognition, we generated molecular models for both RVFV glycoproteins and found significant structural matches between the RVFV Gn protein and the influenza virus hemagglutinin protein and a separate match between RVFV Gc protein and Sindbis virus envelope protein E1. Using these models, the potential interaction and arrangement of both glycoproteins in the RVFV particle was analyzed, by modeling their placement within the cryo-electron microscopy density map of RVFV. We identified four possible arrangements of the glycoproteins in the virion envelope. Each assembly model proposes that the ectodomain of Gn forms the majority of the protruding capsomer and that Gc is involved in formation of the capsomer base. Furthermore, Gc is suggested to facilitate intercapsomer connections. The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins. Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.

Original languageEnglish (US)
Article numberArticle 254
JournalFrontiers in Microbiology
Volume3
Issue numberJUL
DOIs
StatePublished - 2012

Fingerprint

Rift Valley fever virus
Glycoproteins
Orthobunyavirus
Virion
Proteins
Phlebovirus
Sindbis Virus
Alphavirus
Viral Envelope Proteins
Viruses
Cryoelectron Microscopy
Molecular Models
Hemagglutinins
Livestock
Orthomyxoviridae
Antiviral Agents
Antigens

Keywords

  • Bunyavirus assembly
  • Hybrid modeling
  • Multi-body refinement
  • Multi-resolution registration
  • Protein structure prediction

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Rusu, M., Bonneau, R., Holbrook, M. R., Watowich, S., Birmanns, S., Wriggers, W., & Freiberg, A. (2012). An assembly model of Rift Valley fever virus. Frontiers in Microbiology, 3(JUL), [Article 254]. https://doi.org/10.3389/fmicb.2012.00254

An assembly model of Rift Valley fever virus. / Rusu, Mirabela; Bonneau, Richard; Holbrook, Michael R.; Watowich, Stanley; Birmanns, Stefan; Wriggers, Willy; Freiberg, Alexander.

In: Frontiers in Microbiology, Vol. 3, No. JUL, Article 254, 2012.

Research output: Contribution to journalArticle

Rusu, M, Bonneau, R, Holbrook, MR, Watowich, S, Birmanns, S, Wriggers, W & Freiberg, A 2012, 'An assembly model of Rift Valley fever virus', Frontiers in Microbiology, vol. 3, no. JUL, Article 254. https://doi.org/10.3389/fmicb.2012.00254
Rusu M, Bonneau R, Holbrook MR, Watowich S, Birmanns S, Wriggers W et al. An assembly model of Rift Valley fever virus. Frontiers in Microbiology. 2012;3(JUL). Article 254. https://doi.org/10.3389/fmicb.2012.00254
Rusu, Mirabela ; Bonneau, Richard ; Holbrook, Michael R. ; Watowich, Stanley ; Birmanns, Stefan ; Wriggers, Willy ; Freiberg, Alexander. / An assembly model of Rift Valley fever virus. In: Frontiers in Microbiology. 2012 ; Vol. 3, No. JUL.
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