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

Authors

  • Serena Montagnaro,

    1. Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Roberto Ciarcia,

    1. Department of Structures, Functions and Biological Technology, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Francesco Pagnini,

    1. Department of Structures, Functions and Biological Technology, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Luisa De Martino,

    1. Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Maria Valeria Puzio,

    1. Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Giovanna Elvira Granato,

    1. Department of Structures, Functions and Biological Technology, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
    2. Center of Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, BioLife Science Bldg. Suite 333, 1900 N, 12th Street, Philadelphia, Pennsylvania 19122A
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  • Franca Avino,

    1. Human Pathology and Oncology Department, University of Siena, Viale Bracci 2, 53100 Siena, Italy
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  • Ugo Pagnini,

    Corresponding author
    1. Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
    • Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Napoli, Italy.
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  • Giuseppe Iovane,

    1. Department of Pathology and Animal Health, School of Veterinary Medicine, University of Naples, Federico II, Via Delpino n°1, 80137 Naples, Italy
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  • Antonio Giordano

    1. Center of Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, BioLife Science Bldg. Suite 333, 1900 N, 12th Street, Philadelphia, Pennsylvania 19122A
    2. Department of Surgical Oncology and Breast, National Institute of Cancer G. Pascale Foundation, Via Mariano Semmola, 80131 Naples, Italy
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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. J. Cell. Biochem. 114: 1529–1535, 2013. © 2013 Wiley Periodicals, Inc.

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