A TRUSTED targeted mass spectrometry assay for pan-herpesvirus protein detection

Michelle A. Kennedy, Matthew D. Tyl, Cora N. Betsinger, Joel D. Federspiel, Xinlei Sheng, Jesse H. Arbuckle, Thomas M. Kristie, Ileana M. Cristea

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The presence and abundance of viral proteins within host cells are part of the essential signatures of the cellular stages of viral infections. However, methods that can comprehensively detect and quantify these proteins are still limited, particularly for viruses with large protein coding capacity. Here, we design and experimentally validate a mass spectrometry-based Targeted herpesviRUS proTEin Detection (TRUSTED) assay for monitoring human viruses representing the three Herpesviridae subfamilies—herpes simplex virus type 1, human cytomegalovirus (HCMV), and Kaposi sarcoma-associated herpesvirus. We demonstrate assay applicability for (1) capturing the temporal cascades of viral replication, (2) detecting proteins throughout a range of virus concentrations and in in vivo models of infection, (3) assessing the effects of clinical therapeutic agents and sirtuin-modulating compounds, (4) studies using different laboratory and clinical viral strains, and (5) discovering a role for carbamoyl phosphate synthetase 1 in supporting HCMV replication.

Original languageEnglish (US)
Article number110810
JournalCell Reports
Issue number6
StatePublished - May 10 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


  • CP: Microbiology
  • CPS1
  • HCMV
  • HSV-1
  • KSHV
  • PRM
  • herpesvirus
  • mass spectrometry
  • targeted MS
  • virus detection
  • virus protein detection


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