Related Experiment Video
Updated: Jan 6, 2026
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for
Zina M Uckeley1, Rebecca Moeller2, Lars I Kühn3
1CellNetworks Cluster of Excellence and Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany; CellNetworks Cluster of Excellence and Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
Novel 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 immunoprecipitated 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 requires nuclear steps. 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.
Insights
This study reveals that Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) is essential for Uukuniemi virus (UUKV) replication and particle assembly. GBF1 also supports infection by many other RNA viruses, highlighting its broad proviral role.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Novel tick-borne phleboviruses, including Uukuniemi virus (UUKV), are emerging and pose significant human health risks.
- The cellular mechanisms governing phlebovirus assembly, budding, and egress remain poorly understood.
Purpose of the Study:
- To identify host factors involved in Uukuniemi virus (UUKV) infection and assembly.
- To elucidate the role of identified host factors in the viral life cycle.
- To investigate the broader role of these factors in the infection of other RNA viruses.
Main Methods:
- High-resolution, label-free mass spectrometry was used to identify UUKV-interacting cellular partners.
- RNA interference was employed to validate the importance of host factors for UUKV infection.
- GBF1 was inhibited using Golgicide A to confirm its role.
- The study extended to investigate GBF1's role in infections by other viral families.
Main Results:
- Thirty-nine cellular partners interacting with UUKV envelope glycoproteins were identified.
- Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) was identified as a critical host factor for UUKV replication and particle assembly.
- GBF1 inhibition confirmed its essential role in the UUKV life cycle.
- GBF1 was found to be essential for the infection of various RNA viruses, including Flaviviridae, Coronaviridae, Rhabdoviridae, and Togaviridae.
- GBF1 was not essential for adenovirus and retrovirus infections, which involve nuclear steps.
Conclusions:
- Uukuniemi virus (UUKV) critically relies on Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) for its replication, assembly, and egress.
- GBF1 plays a proviral role in the infection of a wide range of zoonotic RNA viruses.
- This highlights GBF1 as a potential therapeutic target for multiple viral infections.
