@article{2af3548c846244beb2c6cda16f0482aa,
title = "A TRUSTED targeted mass spectrometry assay for pan-herpesvirus protein detection",
abstract = "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.",
keywords = "CP: Microbiology, CPS1, HCMV, HSV-1, KSHV, PRM, herpesvirus, mass spectrometry, targeted MS, virus detection, virus protein detection",
author = "Kennedy, {Michelle A.} and Tyl, {Matthew D.} and Betsinger, {Cora N.} and Federspiel, {Joel D.} and Xinlei Sheng and Arbuckle, {Jesse H.} and Kristie, {Thomas M.} and Cristea, {Ileana M.}",
note = "Funding Information: We are grateful for funding provided by NIH NIGMS (GM114141), Stand Up To Cancer Convergence 3.1416, and the Edward Mallinckrodt, Jr. Foundation to I.M.C. NSF Graduate Research Fellowship (DGE-1656466) to M.A.K, NIH Ruth L. Kirschstein F31 fellowship to C.N.B. (1F31AI154796-01A1), the Intramural Research Program of NIAID to T.M.K, and the NIGMS training grant (T32GM007388). We also thank the Molecular Biology Confocal Imaging Facility at Princeton University, a Nikon Center of Excellence, for instrument use and technical advice. Conceptualization, J.D.F. I.M.C. and M.A.K; methodology, J.D.F. and M.A.K.; investigation, M.A.K. J.D.F, C.N.B. M.D.T. X.S. and J.H.A.; software and formal analysis, M.A.K.; data curation, M.A.K. and M.D.T.; writing – original draft, M.A.K. I.M.C. M.D.T. J.D.F. and C.N.B.; Visualization, M.A.K.; writing – review and editing, M.A.K. I.M.C. M.D.T. C.N.B. J.D.F. X.S. J.H.A. and T.M.K.; supervision, I.M.C and T.M.K.; funding acquisition, I.M.C. T.M.K. M.A.K. and C.N.B. I.M.C. is a shareholder of Evrys Bio (previously Forge Life Science), which has licensed sirtuin-related technology from Princeton University. I.M.C. J.D.F. and M.A.K. have a provisional patent application on a “Method for quantitative monitoring of the progression of infections with herpesviruses.” Funding Information: We are grateful for funding provided by NIH NIGMS ( GM114141 ), Stand Up To Cancer Convergence 3.1416, and the Edward Mallinckrodt, Jr. Foundation to I.M.C., NSF Graduate Research Fellowship ( DGE-1656466 ) to M.A.K, NIH Ruth L. Kirschstein F31 fellowship to C.N.B. ( 1F31AI154796-01A1 ), the Intramural Research Program of NIAID to T.M.K, and the NIGMS training grant ( T32GM007388 ). We also thank the Molecular Biology Confocal Imaging Facility at Princeton University, a Nikon Center of Excellence, for instrument use and technical advice. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "10",
doi = "10.1016/j.celrep.2022.110810",
language = "English (US)",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}