Format

Send to

Choose Destination
Mol Cell Proteomics. 2017 Nov;16(11):1990-2005. doi: 10.1074/mcp.M117.067355. Epub 2017 Aug 29.

Phosphoproteomic Analysis Reveals the Importance of Kinase Regulation During Orbivirus Infection.

Author information

1
From the ‡Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
2
§University of Cambridge, Division of Virology, Department of Pathology, Lab block level 5, Box 237, Addenbrookes Hospital, Cambridge, UK.
3
From the ‡Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK; polly.roy@lshtm.ac.uk.

Abstract

Bluetongue virus (BTV) causes infections in wild and domesticated ruminants with high morbidity and mortality and is responsible for significant economic losses in both developing and developed countries. BTV serves as a model for the study of other members of the Orbivirus genus. Previously, the importance of casein kinase 2 for BTV replication was demonstrated. To identify intracellular signaling pathways and novel host-cell kinases involved during BTV infection, the phosphoproteome of BTV infected cells was analyzed. Over 1000 phosphosites were identified using mass spectrometry, which were then used to determine the corresponding kinases involved during BTV infection. This analysis yielded protein kinase A (PKA) as a novel kinase activated during BTV infection. Subsequently, the importance of PKA for BTV infection was validated using a PKA inhibitor and activator. Our data confirmed that PKA was essential for efficient viral growth. Further, we showed that PKA is also required for infection of equid cells by African horse sickness virus, another member of the Orbivirus genus. Thus, despite their preference in specific host species, orbiviruses may utilize the same host signaling pathways during their replication.

PMID:
28851738
PMCID:
PMC5672004
DOI:
10.1074/mcp.M117.067355
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center