DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB)

Abstract

Classical swine fever virus (CSFV) E2 protein, the major virus structural glycoprotein, is an essential component of the viral envelope. E2 is involved in virus absorption, induction of a protective immune response and is critical for virulence in swine. Using the yeast two-hybrid system, we identified protein phosphatase 1 catalytic subunit beta (PPP1CB), which is part of the Protein Phosphatase 1 (PP1) complex, as a specific binding host partner for E2. We further confirmed the occurrence of this interaction in CSFV-infected swine cells by using two independent methodologies: Co-immunoprecipitation and Proximity Ligation Assay. In addition, we demonstrated that pharmacological activation of the PP1 pathway has a negative effect on CSFV replication while inhibition of the PP1 pathway or knockdown of PPP1CB by siRNA had no observed effect. Overall, our data suggests that the CSFV E2 and PPP1CB protein interact in infected cells, and that activation of the PP1 pathway decreases virus replication.

Authors:
 [1];  [2];  [3];  [4];  [3]; ORCiD logo [3]
  1. USDA, Greenport, NY (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
  2. USDA, Greenport, NY (United States); Univ. of Connecticut, Storrs, CT (United States)
  3. USDA, Greenport, NY (United States)
  4. USDA, Greenport, NY (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); Johns Hopkins Applied Physics Lab., Laurel, MD (United States)
Publication Date:
Research Org.:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1580724
Grant/Contract Number:  
SC0014664
Resource Type:
Accepted Manuscript
Journal Name:
Viruses
Additional Journal Information:
Journal Volume: 11; Journal Issue: 4; Journal ID: ISSN 1999-4915
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; E2; classical swine fever virus; CSFV; Viral-Host protein interactions

Citation Formats

Vuono, Elizabeth A., Ramirez-Medina, Elizabeth, Holinka, Lauren G., Baker-Branstetter, Ryan, Borca, Manuel V., and Gladue, Douglas P. Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB). United States: N. p., 2019. Web. doi:10.3390/v11040307.
Vuono, Elizabeth A., Ramirez-Medina, Elizabeth, Holinka, Lauren G., Baker-Branstetter, Ryan, Borca, Manuel V., & Gladue, Douglas P. Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB). United States. https://doi.org/10.3390/v11040307
Vuono, Elizabeth A., Ramirez-Medina, Elizabeth, Holinka, Lauren G., Baker-Branstetter, Ryan, Borca, Manuel V., and Gladue, Douglas P. Fri . "Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB)". United States. https://doi.org/10.3390/v11040307. https://www.osti.gov/servlets/purl/1580724.
@article{osti_1580724,
title = {Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB)},
author = {Vuono, Elizabeth A. and Ramirez-Medina, Elizabeth and Holinka, Lauren G. and Baker-Branstetter, Ryan and Borca, Manuel V. and Gladue, Douglas P.},
abstractNote = {Classical swine fever virus (CSFV) E2 protein, the major virus structural glycoprotein, is an essential component of the viral envelope. E2 is involved in virus absorption, induction of a protective immune response and is critical for virulence in swine. Using the yeast two-hybrid system, we identified protein phosphatase 1 catalytic subunit beta (PPP1CB), which is part of the Protein Phosphatase 1 (PP1) complex, as a specific binding host partner for E2. We further confirmed the occurrence of this interaction in CSFV-infected swine cells by using two independent methodologies: Co-immunoprecipitation and Proximity Ligation Assay. In addition, we demonstrated that pharmacological activation of the PP1 pathway has a negative effect on CSFV replication while inhibition of the PP1 pathway or knockdown of PPP1CB by siRNA had no observed effect. Overall, our data suggests that the CSFV E2 and PPP1CB protein interact in infected cells, and that activation of the PP1 pathway decreases virus replication.},
doi = {10.3390/v11040307},
journal = {Viruses},
number = 4,
volume = 11,
place = {United States},
year = {Fri Mar 29 00:00:00 EDT 2019},
month = {Fri Mar 29 00:00:00 EDT 2019}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Measles Virus Suppresses RIG-I-like Receptor Activation in Dendritic Cells via DC-SIGN-Mediated Inhibition of PP1 Phosphatases
journal, July 2014

  • Mesman, Annelies W.; Zijlstra-Willems, Esther M.; Kaptein, Tanja M.
  • Cell Host & Microbe, Vol. 16, Issue 1
  • DOI: 10.1016/j.chom.2014.06.008

Hemoglobin Subunit Beta Interacts with the Capsid Protein and Antagonizes the Growth of Classical Swine Fever Virus
journal, March 2013


Antagonism of the Phosphatase PP1 by the Measles Virus V Protein Is Required for Innate Immune Escape of MDA5
journal, July 2014


Highly specific detection of phosphorylated proteins by Duolink
journal, September 2009

  • Gullberg, Mats; Andersson, Ann-Catrin
  • Nature Methods, Vol. 6, Issue 9
  • DOI: 10.1038/nmeth.f.267

Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus
journal, January 2014


Role of Protein Phosphatase 1 in Dephosphorylation of Ebola Virus VP30 Protein and Its Targeting for the Inhibition of Viral Transcription
journal, June 2014

  • Ilinykh, Philipp A.; Tigabu, Bersabeh; Ivanov, Andrey
  • Journal of Biological Chemistry, Vol. 289, Issue 33
  • DOI: 10.1074/jbc.M114.575050

Interaction between Core protein of classical swine fever virus with cellular IQGAP1 protein appears essential for virulence in swine
journal, March 2011


Protein Phosphatase-1 regulates Rift Valley fever virus replication
journal, March 2016


The E2 Glycoprotein of Classical Swine Fever Virus Is a Virulence Determinant in Swine
journal, February 2005


Thioredoxin 2 Is a Novel E2-Interacting Protein That Inhibits the Replication of Classical Swine Fever Virus
journal, June 2015

  • Li, Su; Wang, Jinghan; He, Wen-Rui
  • Journal of Virology, Vol. 89, Issue 16
  • DOI: 10.1128/JVI.00429-15

Inhibition of PP1 Phosphatase Activity by HBx: A Mechanism for the Activation of Hepatitis B Virus Transcription
journal, January 2012


Long Chain Ceramides Activate Protein Phosphatase-1 and Protein Phosphatase-2A: ACTIVATION IS STEREOSPECIFIC AND REGULATED BY PHOSPHATIDIC ACID
journal, July 1999

  • Chalfant, Charles E.; Kishikawa, Katsuya; Mumby, Marc C.
  • Journal of Biological Chemistry, Vol. 274, Issue 29
  • DOI: 10.1074/jbc.274.29.20313

Genome Sequence of a Classical Swine Fever Virus of Subgenotype 2.1, Isolated from a Pig in Japan in 2018
journal, January 2019

  • Nishi, Tatsuya; Kameyama, Ken-ichiro; Kato, Tomoko
  • Microbiology Resource Announcements, Vol. 8, Issue 3
  • DOI: 10.1128/MRA.01362-18

Combinatorial control of protein phosphatase-1
journal, July 2001


Identification of a novel virulence determinant within the E2 structural glycoprotein of classical swine fever virus
journal, November 2006


N-Linked Glycosylation Status of Classical Swine Fever Virus Strain Brescia E2 Glycoprotein Influences Virulence in Swine
journal, November 2006

  • Risatti, G. R.; Holinka, L. G.; Fernandez Sainz, I.
  • Journal of Virology, Vol. 81, Issue 2
  • DOI: 10.1128/JVI.01824-06

Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine
journal, November 2010


Direct observation of individual endogenous protein complexes in situ by proximity ligation
journal, October 2006

  • Söderberg, Ola; Gullberg, Mats; Jarvius, Malin
  • Nature Methods, Vol. 3, Issue 12, p. 995-1000
  • DOI: 10.1038/nmeth947

Mutations in the carboxyl terminal region of E2 glycoprotein of classical swine fever virus are responsible for viral attenuation in swine
journal, August 2007


Interaction of CSFV E2 Protein with Swine Host Factors as Detected by Yeast Two-Hybrid System
journal, January 2014


RSV hijacks cellular protein phosphatase 1 to regulate M2-1 phosphorylation and viral transcription
journal, February 2018


HIV-1 Protein Tat1–72 Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway
journal, May 2018


The extended PP1 toolkit: designed to create specificity
journal, August 2010

  • Bollen, Mathieu; Peti, Wolfgang; Ragusa, Michael J.
  • Trends in Biochemical Sciences, Vol. 35, Issue 8
  • DOI: 10.1016/j.tibs.2010.03.002

Sequence and structure-based prediction of eukaryotic protein phosphorylation sites
journal, December 1999

  • Blom, Nikolaj; Gammeltoft, Steen; Brunak, Søren
  • Journal of Molecular Biology, Vol. 294, Issue 5
  • DOI: 10.1006/jmbi.1999.3310

The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus
journal, February 2015

  • Chen, Jianing; He, Wen-Rui; Shen, Liang
  • Journal of Virology, Vol. 89, Issue 9
  • DOI: 10.1128/JVI.00019-15

Nuclear Targeting of Protein Phosphatase-1 by HIV-1 Tat Protein
journal, August 2005

  • Ammosova, Tatyana; Jerebtsova, Marina; Beullens, Monique
  • Journal of Biological Chemistry, Vol. 280, Issue 43
  • DOI: 10.1074/jbc.M503673200

Mutation of E1 glycoprotein of classical swine fever virus affects viral virulence in swine
journal, December 2005


Antigenic structure of envelope glycoprotein E1 of hog cholera virus
journal, June 1994


An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene.
journal, January 1996


Antagonism of the Phosphatase PP1 by the Measles Virus V Protein Is Required for Innate Immune Escape of MDA5
journal, July 2014


The extended PP1 toolkit: designed to create specificity
journal, August 2010

  • Bollen, Mathieu; Peti, Wolfgang; Ragusa, Michael J.
  • Trends in Biochemical Sciences, Vol. 35, Issue 8
  • DOI: 10.1016/j.tibs.2010.03.002

Mutation of E1 glycoprotein of classical swine fever virus affects viral virulence in swine
journal, December 2005


Identification of a novel virulence determinant within the E2 structural glycoprotein of classical swine fever virus
journal, November 2006


Degeneracy and Function of the Ubiquitous RV X F Motif That Mediates Binding to Protein Phosphatase-1
journal, March 2003

  • Wakula, Paulina; Beullens, Monique; Ceulemans, Hugo
  • Journal of Biological Chemistry, Vol. 278, Issue 21
  • DOI: 10.1074/jbc.m300175200

Mutations Abrogating the RNase Activity in Glycoprotein E rns of the Pestivirus Classical Swine Fever Virus Lead to Virus Attenuation
journal, December 1999


Works referencing / citing this record:

Structural Glycoprotein E2 of Classical Swine Fever Virus Interacts with Host Protein Dynactin Subunit 6 (DCTN6) during the Virus Infectious Cycle
journal, October 2019

  • Borca, M. V.; Vuono, E. A.; Ramirez-Medina, E.
  • Journal of Virology, Vol. 94, Issue 1
  • DOI: 10.1128/jvi.01642-19