Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line

Serena Montagnaro, Roberto Ciarcia, Francesco Pagnini, Luisa De Martino, Maria Valeria Puzio, Giovanna Elvira Granato, Franca Avino, Ugo Pagnini, Giuseppe Iovane, Antonio Giordano

Research output: Contribution to journalArticle

Abstract

Bovine herpesvirus type 4 (BoHV-4), like other herpesviruses, induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of BoHV-4 infection on autophagy in BoHV-4 infected Madin Darby bovine kidney (MDBK) cells. Protein extracts of BoHV-4 infected and control MDBK cells were subjected to Western blot. The concentrations of the autophagy and apoptosis-related proteins Beclin 1, p21, PI3 kinase, Akt1/2, mTOR, phospho mTOR, p62 and the light chain three (LC3) were normalized to the actin level and expressed as the densitometric ratio. Western blot analysis of virus-infected cells revealed that autophagic degradation pathway was induced in the late phase of BoHV-4 infection. After 48 h post-infection the protein LC3II, which is essential for autophagy was found to be markedly increased, while infection of MDBK cells with BoHV-4 resulted in a depletion of p62 levels. Becline 1, PI3 kinase, Akt1/2 and p21 expression increased between 24 and 48 h post-infection. Surprisingly, mTOR and its phosphorylated form, which are negative regulators of autophagy, also increased after 24 h post-infection. In conclusion, our findings suggest that BoHV-4 has developed mechanisms for modulation of autophagy that are probably part of a strategy designed to enhance viral replication and to evade the immune system. Additional studies on the relationship between autophagy and BoHV-4 replication and survival, in both lytic and latent replication phases, are needed to understand the role of autophagy in BoHV-4 pathogenesis.

Original languageEnglish
Pages (from-to)1529-1535
Number of pages7
JournalJournal of Cellular Biochemistry
Volume114
Issue number7
DOIs
Publication statusPublished - Jul 2013

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Bovine Herpesvirus 4
Herpesviridae Infections
Autophagy
Cells
Phosphatidylinositol 3-Kinases
Cell Line
Proteins
Immune system
Viruses
Actins
Modulation
Apoptosis
Infection
Kidney
Degradation
Western Blotting
Herpesviridae
Immune System

Keywords

  • AUTOPHAGIC FLUX
  • AUTOPHAGY
  • BOVINE HERPESVIRUS 4
  • WESTERN BLOT ASSAY

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Montagnaro, S., Ciarcia, R., Pagnini, F., De Martino, L., Puzio, M. V., Granato, G. E., ... Giordano, A. (2013). Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line. Journal of Cellular Biochemistry, 114(7), 1529-1535. https://doi.org/10.1002/jcb.24494

Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line. / Montagnaro, Serena; Ciarcia, Roberto; Pagnini, Francesco; De Martino, Luisa; Puzio, Maria Valeria; Granato, Giovanna Elvira; Avino, Franca; Pagnini, Ugo; Iovane, Giuseppe; Giordano, Antonio.

In: Journal of Cellular Biochemistry, Vol. 114, No. 7, 07.2013, p. 1529-1535.

Research output: Contribution to journalArticle

Montagnaro, S, Ciarcia, R, Pagnini, F, De Martino, L, Puzio, MV, Granato, GE, Avino, F, Pagnini, U, Iovane, G & Giordano, A 2013, 'Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line', Journal of Cellular Biochemistry, vol. 114, no. 7, pp. 1529-1535. https://doi.org/10.1002/jcb.24494
Montagnaro S, Ciarcia R, Pagnini F, De Martino L, Puzio MV, Granato GE et al. Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line. Journal of Cellular Biochemistry. 2013 Jul;114(7):1529-1535. https://doi.org/10.1002/jcb.24494
Montagnaro, Serena ; Ciarcia, Roberto ; Pagnini, Francesco ; De Martino, Luisa ; Puzio, Maria Valeria ; Granato, Giovanna Elvira ; Avino, Franca ; Pagnini, Ugo ; Iovane, Giuseppe ; Giordano, Antonio. / Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 7. pp. 1529-1535.
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abstract = "Bovine herpesvirus type 4 (BoHV-4), like other herpesviruses, induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of BoHV-4 infection on autophagy in BoHV-4 infected Madin Darby bovine kidney (MDBK) cells. Protein extracts of BoHV-4 infected and control MDBK cells were subjected to Western blot. The concentrations of the autophagy and apoptosis-related proteins Beclin 1, p21, PI3 kinase, Akt1/2, mTOR, phospho mTOR, p62 and the light chain three (LC3) were normalized to the actin level and expressed as the densitometric ratio. Western blot analysis of virus-infected cells revealed that autophagic degradation pathway was induced in the late phase of BoHV-4 infection. After 48 h post-infection the protein LC3II, which is essential for autophagy was found to be markedly increased, while infection of MDBK cells with BoHV-4 resulted in a depletion of p62 levels. Becline 1, PI3 kinase, Akt1/2 and p21 expression increased between 24 and 48 h post-infection. Surprisingly, mTOR and its phosphorylated form, which are negative regulators of autophagy, also increased after 24 h post-infection. In conclusion, our findings suggest that BoHV-4 has developed mechanisms for modulation of autophagy that are probably part of a strategy designed to enhance viral replication and to evade the immune system. Additional studies on the relationship between autophagy and BoHV-4 replication and survival, in both lytic and latent replication phases, are needed to understand the role of autophagy in BoHV-4 pathogenesis.",
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