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

doi:10.1016/j.celrep.2022.110810

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 journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Article number	110810
Journal	Cell Reports
Volume	39
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2022.110810
State	Published - May 10 2022

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

Keywords

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

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10.1016/j.celrep.2022.110810

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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.}",

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doi = "10.1016/j.celrep.2022.110810",

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AU - Kennedy, Michelle A.

AU - Tyl, Matthew D.

AU - Betsinger, Cora N.

AU - Federspiel, Joel D.

AU - Sheng, Xinlei

AU - Arbuckle, Jesse H.

AU - Kristie, Thomas M.

AU - Cristea, Ileana M.

PY - 2022/5/10

Y1 - 2022/5/10

N2 - 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.

AB - 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.

KW - CP: Microbiology

KW - CPS1

KW - HCMV

KW - HSV-1

KW - KSHV

KW - PRM

KW - herpesvirus

KW - mass spectrometry

KW - targeted MS

KW - virus detection

KW - virus protein detection

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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