Rapid Degradation Pathways of Host Proteins During HCMV Infection Revealed by Quantitative Proteomics.
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Publication Date
2020Journal Title
Front Cell Infect Microbiol
ISSN
2235-2988
Publisher
Frontiers Media SA
Volume
10
Pages
578259
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic-eCollection
Metadata
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Lin, K., Nightingale, K., Soday, L., Antrobus, R., & Weekes, M. (2020). Rapid Degradation Pathways of Host Proteins During HCMV Infection Revealed by Quantitative Proteomics.. Front Cell Infect Microbiol, 10 578259. https://doi.org/10.3389/fcimb.2020.578259
Abstract
Human cytomegalovirus (HCMV) is an important pathogen in immunocompromised individuals and neonates, and a paradigm for viral immune evasion. We previously developed a quantitative proteomic approach that identified 133 proteins degraded during the early phase of HCMV infection, including known and novel antiviral factors. The majority were rescued from degradation by MG132, which is known to inhibit lysosomal cathepsins in addition to the proteasome. Global definition of the precise mechanisms of host protein degradation is important both to improve our understanding of viral biology, and to inform novel antiviral therapeutic strategies. We therefore developed and optimized a multiplexed comparative proteomic analysis using the selective proteasome inhibitor bortezomib in addition to MG132, to provide a global mechanistic view of protein degradation. Of proteins rescued from degradation by MG132, 34-47 proteins were also rescued by bortezomib, suggesting both that the predominant mechanism of protein degradation employed by HCMV is via the proteasome, and that alternative pathways for degradation are nevertheless important. Our approach and data will enable improved mechanistic understanding of HCMV and other viruses, and provide a shortlist of candidate restriction factors for further analysis.
Keywords
Humans, Cytomegalovirus, Proteins, Proteomics, Infant, Newborn, Immune Evasion, Proteolysis
Sponsorship
Wellcome Trust (108070/Z/15/Z)
Wellcome Trust (100140/Z/12/Z)
Identifiers
External DOI: https://doi.org/10.3389/fcimb.2020.578259
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318097
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