Phosphorylation of the bovine papillomavirus E2 protein on tyrosine regulates its transcription and replication functions

Sara P. Culleton, Sriramana Kanginakudru, Marsha DeSmet, Timra Gilson, Fang Xie, Shwu Yuan Wu, Cheng Ming Chiang, Guihong Qi, Mu Wang, Elliot J. Androphy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Papillomaviruses are small, double-stranded DNA viruses that encode the E2 protein, which controls transcription, replication, and genome maintenance in infected cells. Posttranslational modifications (PTMs) affecting E2 function and stability have been demonstrated for multiple types of papillomaviruses. Here we describe the first phosphorylation event involving a conserved tyrosine (Y) in the bovine papillomavirus 1 (BPV-1) E2 protein at amino acid 102. While its phosphodeficient phenylalanine (F) mutant activated both transcription and replication in luciferase reporter assays, a mutant that may act as a phosphomimetic, with a Y102-toglutamate (E) mutation, lost both activities. The E2 Y102F protein interacted with cellular E2-binding factors and the viral helicase E1; however, in contrast, the Y102E mutant associated with only a subset and was unable to bind to E1. While the Y102F mutant fully supported transient viral DNA replication, BPV genomes encoding this mutation as well as Y102E were not maintained as stable episomes in murine C127 cells. These data imply that phosphorylation at Y102 disrupts the helical fold of the N-terminal region of E2 and its interaction with key cellular and viral proteins. We hypothesize that the resulting inhibition of viral transcription and replication in basal epithelial cells prevents the development of a lytic infection.

Original languageEnglish (US)
Article numbere01854-16
JournalJournal of virology
Volume91
Issue number2
DOIs
StatePublished - 2017

Keywords

  • Papillomavirus
  • Papillomavirus E2
  • Tyrosine phosphorylation
  • Viral replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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