Quantitative proteomics of Uukuniemi virus - host cell interactions reveals GBF1 as proviral host factor for phleboviruses.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsUckeley, Zina M
Kühn, Lars I
Överby, Anna K
MetadataShow full item record
AbstractNovel tick-borne phleboviruses in the Phenuiviridae family, which are highly pathogenic in humans and all closely related to Uukuniemi virus (UUKV), have recently emerged on different continents. How phleboviruses assemble, bud, and exit cells remains largely elusive. Here, we performed high-resolution, label-free mass spectrometry analysis of UUKV immuno-precipitated from cell lysates and identified 39 cellular partners interacting with the viral envelope glycoproteins. The importance of these host factors for UUKV infection was validated by silencing each host factor by RNA interference. This revealed Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1), a guanine nucleotide exchange factor resident in the Golgi, as a critical host factor required for the UUKV life cycle. An inhibitor of GBF1, Golgicide A, confirmed the role of the cellular factor in UUKV infection. We could pinpoint the GBF1 requirement to UUKV replication and particle assembly. When the investigation was extended to viruses from various positive and negative RNA viral families, we found that not only phleboviruses rely on GBF1 for infection, but also Flavi-, Corona-, Rhabdo-, and Togaviridae In contrast, silencing or blocking GBF1 did not abrogate infection by the human adenovirus serotype 5 and immunodeficiency retrovirus type 1, the replication of both occurs in the nucleus. Together our results indicate that UUKV relies on GBF1 for viral replication, assembly and egress. This study also highlights the proviral activity of GBF1 in the infection by a broad range of important zoonotic RNA viruses.
CitationMol Cell Proteomics. 2019 Sep 30. pii: RA119.001631. doi: 10.1074/mcp.RA119.001631.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Generation of mutant Uukuniemi viruses lacking the nonstructural protein NSs by reverse genetics indicates that NSs is a weak interferon antagonist.
- Authors: Rezelj VV, Överby AK, Elliott RM
- Issue date: 2015 May
- Uukuniemi Virus as a Tick-Borne Virus Model.
- Authors: Mazelier M, Rouxel RN, Zumstein M, Mancini R, Bell-Sakyi L, Lozach PY
- Issue date: 2016 Aug 1
- Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles.
- Authors: Vonderstein K, Nilsson E, Hubel P, Nygård Skalman L, Upadhyay A, Pasto J, Pichlmair A, Lundmark R, Överby AK
- Issue date: 2018 Jan 1
- The Guanine Nucleotide Exchange Factor GBF1 Participates in Rotavirus Replication.
- Authors: Martínez JL, Arnoldi F, Schraner EM, Eichwald C, Silva-Ayala D, Lee E, Sztul E, Burrone ÓR, López S, Arias CF
- Issue date: 2019 Oct 1
- Investigation of the role of GBF1 in the replication of positive-sense single-stranded RNA viruses.
- Authors: Ferlin J, Farhat R, Belouzard S, Cocquerel L, Bertin A, Hober D, Dubuisson J, Rouillé Y
- Issue date: 2018 Aug