HSV-1 VP11/12-mediated initiation of Src family kinase-PI3 kinase-Akt signalling

• Author / Creator

  Wu, Frederick W

• Herpes simplex virus type 1 is a ubiquitous human virus that causes cold sores and, increasingly, genital herpes. Upon virion-cell fusion, tegument proteins diffuse into host cytosol and, as such, are poised to remodel signalling pathways. Tegument proteins of interest here are virion protein 11/12 (VP11/12) and US3 protein kinase (US3PK), for its potential role in VP11/12 regulation. Wagner and Smiley (2011) posited a model wherein VP11/12 commandeers Lck to activate Akt. This study tests this model using various in vitro assays to dissect VP11/12 interaction with the Lck SH2 domain. My findings support the Wagner-Smiley model. To address curiosities in prior US3PK characterization, I generated US3-null mutants from wild-type and UL46-null viruses to produce US3- and UL46-null single and double knock-outs derived from KOS-37. Preliminary analysis of US3 mutants shows US3PK-dependent VP11/12 modification. These mutants allow for further exploration of US3PK-VP11/12 interplay.

• Subjects / Keywords

  • SH2
  • Src family kinase activation
  • Lck
  • Herpes
  • HSV
  • VP11/12
  • HHV
  • Peptide competition assay

• Graduation date

  Fall 2013

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3KH3F

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.