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Proteomic and phosphoproteomic analyses reveal several events involved in the early stages of bovine herpesvirus 1 infection

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Abstract

Herpesviruses are predicted to express more than 80 proteins during their infection cycle. The proteins synthesized by the immediate early genes and early genes target signaling pathways in host cells that are essential for the successful initiation of a productive infection and for latency. In this study, proteomic and phosphoproteomic tools showed the occurrence of changes in Madin-Darby bovine kidney cells at the early stage of the infection by bovine herpesvirus 1 (BoHV-1). Proteins that had already been described in the early stage of infection for other herpesviruses but not for BoHV-1 were found. For example, stathmin phosphorylation at the initial stage of infection is described for the first time. In addition, two proteins that had not been described yet in the early stages of herpesvirus infections in general were ribonuclease/angiogenin inhibitor and Rab GDP dissociation inhibitor beta. The biological processes involved in these cellular responses were repair and replication of DNA, splicing, microtubule dynamics, and inflammatory responses. These results reveal pathways that might be used as targets for designing antiviral molecules against BoHV-1 infection.

Highlights

  • BoHV-1 infection at early stages influenced various biological processes.

  • BoHV-1 infection at early stages showed proteins reported for other virus and stages.

  • Proteins not yet reported for BoHV-1 infection in the early stage were ribonuclease/angiogenin inhibitor and Rab GDP dissociation inhibitor beta

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Abbreviations

2-DE:

two-dimensional gel electrophoresis

ACN:

acetonitrile

ACTB:

beta-actin

AHSG:

alpha-2-HS glycoprotein

Apo-AI:

apolipoprotein A-I

BoHV-1:

bovine herpesvirus 1

BRDC:

bovine respiratory disease complex

C1/C2:

heterogeneous nuclear ribonucleoprotein C

CHAPS:

3-3-cholamidopropyl dimethylammonio-1-propanesulfonate

CyHV-2:

cyprinid herpesvirus 2

DTT:

dithiothreitol

DUT:

deoxyuridine triphosphate

dUTPase:

deoxyuridine triphosphatase

EBNA2:

Epstein-Barr virus nuclear antigen 2

EG:

early gene

FA:

formic acid

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

Grp78:

78 kDa glucose-regulated protein

HHV-1:

human herpesvirus 1

HNRNPK:

heterogeneous nuclear ribonucleoprotein K

hpi:

hours postinfection

HSP27:

heat shock protein beta-1

HSP70:

heat shock protein 70

HVEM:

HHV-1 entry mediator

IEG:

immediate-early gene

IPG:

immobilized pH gradient

LG:

late gene

MDBK:

Madin-Darby bovine kidney

MEM:

minimum essential medium

MOI:

multiplicity of infection

MS:

mass spectrometry

NPM:

nucleophosmin

NPM1:

nucleophosmin-1

OSF1:

osteoclast stimulating factor

PCNA:

proliferating cell nuclear antigen

PNP:

purine nucleoside phosphorylase

PTGES3:

prostaglandin E synthase 3

qPCR:

real-time quantitative PCR

RNH1:

ribonuclease/angiogenin inhibitor 1

RPLP0:

ribosomal protein large P0

RPS18:

ribosomal protein S18

SR:

serine/arginine-rich

STMN1:

stathmin 1

TBB:

tubulin beta

TFA:

trifluoroacetic acid

VHS:

virion host shut-off

vRNP:

viral ribonucleoproteins

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Acknowledgements

The authors thank the Brazilian Agencies Foundation for Research Support of Minas Gerais (FAPEMIG: Fellowships and Grants, PPM-00796-15), the Financier of Studies and Projects (FINEP: CT-INFRA/UFV-2004/2007/2008), the National Council for Scientific and Technological Development (CNPq: Grants: 483976/2012-1 and 455318/2014-0), and Coordination for the Improvement of Higher Education Personnel (CAPES: Fellowships) for financial support. The authors would like to thank Nucleus of Analysis of Biomolecules (NuBioMol, UFV, Viçosa-MG, Brazil) for assistance with mass spectrometric analysis, and the Institute of Biotechnology Applied to Agriculture (BIOAGRO, UFV, Viçosa-MG, Brazil) for technical support. Funding Sources in Brazil: Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) http://dx.doi.org/10.13039/501100004901. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) http://dx.doi.org/10.13039/501100003593. Financiadora de Estudos e Projetos (FINEP) http://dx.doi.org/10.13039/501100004809. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) http://dx.doi.org/10.13039/501100002322.

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Authors and Affiliations

  1. Laboratory of Animal Molecular Infectology, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil

    Marcos J. Magalhães-Junior, Gustavo C. Bressan, Juliana L. R. Fietto & Márcia R. Almeida

  2. Laboratory of Proteomics and Protein Biochemistry, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil

    Marcos J. Magalhães-Junior, Maria Cristina Baracat-Pereira & Lorena K. J. Pereira

  3. Nucleus of Biomolecules Analysis, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil

    Camilo E. Vital

  4. Laboratory of Immunobiology and Animal Virology, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil

    Marcus R. Santos & Abelardo Silva-Júnior

  5. Laboratory of Cell Biology, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil

    Kenner M. Fernandes

  6. Laboratory of Cell and Molecular Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil

    Pricila S. Cunha

  7. Department of Biochemistry and Molecular Biology, Federal University of Viçosa, Viçosa, MG, 36570-900, Brazil

    Maria Cristina Baracat-Pereira

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  1. Marcos J. Magalhães-Junior
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Contributions

MJMJ, LKJP, CEV, and KMF cultured and infected cells, performed electrophoresis assays and protein analysis. MJMJ, PSC and MRS performed real-time PCR. MCBP, ASJ, GCB, JLRF, PSC, MRS, and MRA designed and conducted the biological assays. MJMJ, MCBP, ASJ, PSC, and MRS wrote and revised the manuscript. All authors contributed and gave approval to the final version of the manuscript.

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Correspondence to Maria Cristina Baracat-Pereira.

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Magalhães-Junior, M.J., Baracat-Pereira, M.C., Pereira, L.K.J. et al. Proteomic and phosphoproteomic analyses reveal several events involved in the early stages of bovine herpesvirus 1 infection. Arch Virol 165, 69–85 (2020). https://doi.org/10.1007/s00705-019-04452-1

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