Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

Jeffrey R. Johnson; David C. Crosby; Judd F. Hultquist; Andrew P. Kurland; Prithy Adhikary; Donna Li; John Marlett; Justine Swann; Ruth Hüttenhain; Erik Verschueren; Tasha L. Johnson; Billy W. Newton; Michael Shales; Viviana A. Simon; Pedro Beltrao; Alan D. Frankel; Alexander Marson; Jeffery S. Cox; Oliver I. Fregoso; John A.T. Young; Nevan J. Krogan

doi:10.1016/j.celrep.2022.110690

Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

Jeffrey R. Johnson, David C. Crosby, Judd F. Hultquist, Andrew P. Kurland, Prithy Adhikary, Donna Li, John Marlett, Justine Swann, Ruth Hüttenhain, Erik Verschueren, Tasha L. Johnson, Billy W. Newton, Michael Shales, Viviana A. Simon, Pedro Beltrao, Alan D. Frankel, Alexander Marson, Jeffery S. Cox, Oliver I. Fregoso, John A.T. YoungNevan J. Krogan

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types—phosphorylation and ubiquitination—in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.

Original language	English
Article number	110690
Journal	Cell Reports
Volume	39
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2022.110690
State	Published - 12 Apr 2022

Keywords

CP: Microbiology
CP: Molecular biology
HIV-1
b56
histone h1
phosphorylation
pp2a
proteomics
systems biology
ubiquitination
vif
vpr

Access to Document

10.1016/j.celrep.2022.110690

Cite this

Johnson, J. R., Crosby, D. C., Hultquist, J. F., Kurland, A. P., Adhikary, P., Li, D., Marlett, J., Swann, J., Hüttenhain, R., Verschueren, E., Johnson, T. L., Newton, B. W., Shales, M., Simon, V. A., Beltrao, P., Frankel, A. D., Marson, A., Cox, J. S., Fregoso, O. I., ... Krogan, N. J. (2022). Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling. Cell Reports, 39(2), Article 110690. https://doi.org/10.1016/j.celrep.2022.110690

@article{0d0ec7ac16ac4aa1a30519e8e345cf4f,

title = "Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling",

abstract = "Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types—phosphorylation and ubiquitination—in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.",

keywords = "CP: Microbiology, CP: Molecular biology, HIV-1, b56, histone h1, phosphorylation, pp2a, proteomics, systems biology, ubiquitination, vif, vpr",

author = "Johnson, {Jeffrey R.} and Crosby, {David C.} and Hultquist, {Judd F.} and Kurland, {Andrew P.} and Prithy Adhikary and Donna Li and John Marlett and Justine Swann and Ruth H{\"u}ttenhain and Erik Verschueren and Johnson, {Tasha L.} and Newton, {Billy W.} and Michael Shales and Simon, {Viviana A.} and Pedro Beltrao and Frankel, {Alan D.} and Alexander Marson and Cox, {Jeffery S.} and Fregoso, {Oliver I.} and Young, {John A.T.} and Krogan, {Nevan J.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = apr,

day = "12",

doi = "10.1016/j.celrep.2022.110690",

language = "English",

volume = "39",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "2",

}

Johnson, JR, Crosby, DC, Hultquist, JF, Kurland, AP, Adhikary, P, Li, D, Marlett, J, Swann, J, Hüttenhain, R, Verschueren, E, Johnson, TL, Newton, BW, Shales, M, Simon, VA, Beltrao, P, Frankel, AD, Marson, A, Cox, JS, Fregoso, OI, Young, JAT & Krogan, NJ 2022, 'Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling', Cell Reports, vol. 39, no. 2, 110690. https://doi.org/10.1016/j.celrep.2022.110690

TY - JOUR

T1 - Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

AU - Johnson, Jeffrey R.

AU - Crosby, David C.

AU - Hultquist, Judd F.

AU - Kurland, Andrew P.

AU - Adhikary, Prithy

AU - Li, Donna

AU - Marlett, John

AU - Swann, Justine

AU - Hüttenhain, Ruth

AU - Verschueren, Erik

AU - Johnson, Tasha L.

AU - Newton, Billy W.

AU - Shales, Michael

AU - Simon, Viviana A.

AU - Beltrao, Pedro

AU - Frankel, Alan D.

AU - Marson, Alexander

AU - Cox, Jeffery S.

AU - Fregoso, Oliver I.

AU - Young, John A.T.

AU - Krogan, Nevan J.

PY - 2022/4/12

Y1 - 2022/4/12

N2 - Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types—phosphorylation and ubiquitination—in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.

AB - Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types—phosphorylation and ubiquitination—in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.

KW - CP: Microbiology

KW - CP: Molecular biology

KW - HIV-1

KW - b56

KW - histone h1

KW - phosphorylation

KW - pp2a

KW - proteomics

KW - systems biology

KW - ubiquitination

KW - vif

KW - vpr

UR - http://www.scopus.com/inward/record.url?scp=85128130217&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.110690

DO - 10.1016/j.celrep.2022.110690

M3 - Article

C2 - 35417684

AN - SCOPUS:85128130217

SN - 2211-1247

VL - 39

JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 110690

ER -

Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

Abstract

Keywords

Access to Document

Fingerprint

Cite this