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Porcine reproductive and respiratory syndrome virus envelope (E) protein interacts with mitochondrial proteins and induces apoptosis

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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses for the swine industry worldwide. The PRRSV E protein, encoded by ORF 2b, is one of the non-glycosylated minor structural proteins. In this study, we present evidence for the interaction of the E protein with mitochondrial proteins ATP5A (part of ATP synthase complex), prohibitin, and ADP/ATP translocase. We additionally demonstrate partial mitochondrial localization of the E protein in transfected cells. To functionally investigate these interactions, we infected MARC-145 cells with PRRSV or alphavirus replicon particles (VRPs) expressing PRRSV E protein. In infected cells, production of ATP was significantly reduced. The E protein also induced apoptosis by activating caspase-3, which results in PARP cleavage. Taken together, these data suggest that the PRRSV E protein interacts with mitochondrial proteins and induces apoptosis by inhibiting ATP production.

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Acknowledgments

We thank Dr. Ilya V. Frolov (University of Alabama) for providing plasmids to make VEE VRPs, and Mr. Yurij Popowych for help with flow cytometry analysis. We are thankful to the Saskatchewan Ministry of Agriculture (Agriculture Development Fund) for financial support. This paper was published with the permission of the Director of VIDO-InterVac, journal series no. 755.

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Author notes

  1. Sujit Pujhari

    Present address: Department of Entomology, The Center for Infectious Disease Dynamics, and the Huck Institutes of the Life Sciences, Millennium Science Complex, Pennsylvania State University, University Park, PA, 16802, USA

Authors and Affiliations

  1. Vaccine and Infectious Disease Organization-International Vaccine Center (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3, Canada

    Alexander N. Zakhartchouk

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  1. Sujit Pujhari
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Correspondence to Alexander N. Zakhartchouk.

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The study was funded in part by funding from the Saskatchewan Ministry of Agriculture (ANZ is a principal investigator).

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Pujhari, S., Zakhartchouk, A.N. Porcine reproductive and respiratory syndrome virus envelope (E) protein interacts with mitochondrial proteins and induces apoptosis. Arch Virol 161, 1821–1830 (2016). https://doi.org/10.1007/s00705-016-2845-4

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  • DOI: https://doi.org/10.1007/s00705-016-2845-4

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