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  Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses

Uckeley, Z. M., Moeller, R., Kuhn, L. I., Nilsson, E., Robens, C., Lasswitz, L., et al. (2019). Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. MOLECULAR & CELLULAR PROTEOMICS, 18(12), 2401-2417. doi:10.1074/mcp.RA119.001631.

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 Creators:
Uckeley, Zina M.1, Author
Moeller, Rebecca1, Author
Kuhn, Lars I.2, Author           
Nilsson, Emma1, Author
Robens, Claudia1, Author
Lasswitz, Lisa1, Author
Lindqvist, Richard1, Author
Lenman, Annasara1, Author
Passos, Vania1, Author
Voss, Yannik1, Author
Sommerauer, Christian1, Author
Kampmann, Martin1, Author
Goffinet, Christine1, Author
Meissner, Felix2, Author           
Overby, Anna K.1, Author
Lozach, Pierre-Yves1, Author
Gerold, Gisa1, Author
Affiliations:
1external, ou_persistent22              
2Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: NUCLEOTIDE EXCHANGE FACTOR; BORNE ENCEPHALITIS-VIRUS; SEMLIKI-FOREST-VIRUS; SECRETORY PATHWAY; DC-SIGN; GOLGI; ENTRY; RNA; PLATFORM; FEVERViruses; glycoproteins; affinity proteomics; label-free quantification; peptide mass fingerprinting; assembly; egress; GBF1; replication; Uukuniemi;
 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.
Ticks are important vectors of infectious emerging diseases and tick-borne phleboviruses represent a growing threat to humans globally. We employed here a high-resolution, label-free mass spectrometry and RNA interference screen approach to reveal the host cell protein GBF1 as a proviral factor, not only for tick-borne phleboviruses, but also for many other important zoonotic RNA viruses. This study lays the basis for the development of innovative antiviral strategies against a broad range of human pathogenic viruses.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000501288700005
DOI: 10.1074/mcp.RA119.001631
 Degree: -

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Title: MOLECULAR & CELLULAR PROTEOMICS
Source Genre: Journal
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Publ. Info: 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Pages: - Volume / Issue: 18 (12) Sequence Number: - Start / End Page: 2401 - 2417 Identifier: ISSN: 1535-9476