Comparison of protein expression during wild-type, and E1B-55k-deletion, adenovirus infection using quantitative time-course proteomics

Yen Rong Fu, Andrew S Turnell, Simon Davis, Kate J Heesom, Vanessa C Evans, David A Matthews

Research output: Contribution to journalArticle (Academic Journal)

6 Citations (Scopus)
187 Downloads (Pure)

Abstract

Adenovirus has evolved strategies to usurp host-cell factors and machinery to facilitate its life cycle, including cell entry, replication, assembly and egress. Adenovirus continues, therefore, to be an important model system for investigating fundamental cellular processes. The role of adenovirus E1B-55k in targeting host-cell proteins that possess antiviral activity for proteasomal degradation is now well established. To expand our understanding of E1B-55k in regulating the levels of host-cell proteins, we performed comparative proteome analysis of wild-type, and E1B-55k-deletion, adenovirus-infected cancer cells. As such we performed quantitative MS/MS analysis to monitor protein expression changes affected by viral E1B-55k. We identified 5937 proteins, and of these, 69 and 58 proteins were down-regulated during wild-type and E1B-55k (dl1520) adenovirus infection, respectively. This analysis revealed that there are many, previously unidentified, cellular proteins subjected to degradation by adenovirus utilizing pathways independent of E1B-55k expression. Moreover, we found that ALCAM, EPHA2 and PTPRF, three cellular proteins that function in the regulation of cell-cell contacts, appeared to be degraded by E1B-55k/E4orf3 and/or E1B-55k/E4orf6 complexes. These molecules, like integrin α3 (a known substrate of E1B-55k/E4orf6), are critical regulators of cell signalling, cell adhesion and cell surface modulation, and their degradation during infection is, potentially, pertinent to adenovirus propagation. The data presented in this study illustrate the broad nature of protein down-regulation mediated by adenovirus.

Original languageEnglish
Pages (from-to)1377-1388
Number of pages12
JournalJournal of General Virology
Volume98
Issue number6
Early online date20 Jun 2017
DOIs
Publication statusPublished - 20 Jun 2017

Keywords

  • Adenoviridae
  • Adenoviridae Infections
  • Adenovirus E1B Proteins
  • Cell Line, Tumor
  • Gene Deletion
  • Host-Pathogen Interactions
  • Humans
  • Proteome
  • Proteomics
  • Tandem Mass Spectrometry
  • Time Factors
  • Journal Article

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