Degrading our defenses: novel features of human cytomegalovirus-induced HLA class I ERADication

A.B.C. Schuren

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)


Herpesviruses have evolved various strategies to evade the immune system of their hosts. As a member of the Herpesviridae, human cytomegalovirus (HCMV) evades immune recognition by specifically downregulating antigen-presenting HLA class I molecules.
During its synthesis, HLA class I is translocated into the endoplasmic reticulum (ER), where it is loaded with an antigenic peptide. Once loaded with a peptide, the HLA class I complex travels to the plasma membrane, where it can activate CD8+ T cells.
The HCMV proteins US2 and US11 prevent this by degrading ER-resident HLA class I molecules, hijacking the quality control mechanism for misfolded proteins. In this process, called ER-associated protein degradation (ERAD), misfolded proteins are recognized in the ER and transported back into the cytosol, where they are degraded by the ubiquitin-proteasome system.
The mechanisms of ERAD are complex and only partially understood. With US2- and US11-mediated HLA class I degradation as a model for ERAD, we have screened for and functionally characterized novel components of ER-associated HLA class I degradation.
Original languageEnglish
  • Wiertz, Emmanuel, Primary supervisor
  • Lebbink, Robert Jan, Co-supervisor
Award date2 Apr 2019
Place of Publication[Utrecht]
Print ISBNs978-90-9031492-1
Publication statusPublished - 2 Apr 2019


  • CMV
  • cytomegalovirus
  • HLA
  • immuunevasie
  • immune evasion
  • ERAD
  • ER-associated protein degradation


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