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Porcine reproductive and respiratory syndrome virus modulates apoptosis during replication in alveolar macrophages

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Abstract

Different viruses have evolved strategies that inhibit apoptosis of the host cell early in infection and/or induce apoptosis in the host cell late in infection. In this study, it was investigated if and when porcine reproductive and respiratory syndrome virus (PRRSV) modulates apoptosis in PRRSV-infected macrophages. The PRRSV replication cycle in macrophages was completed within 12 h post-inoculation (hpi). PRRSV-infected macrophages, treated with staurosporine at 4, 5, 6 and 8 hpi, were significantly protected against staurosporine-induced apoptosis, but PRRSV-infected macrophages, treated with staurosporine at 12 hpi, were not. In contrast, starting from 12 hpi, all PRRSV-infected macrophages died by caspase-dependent apoptosis, which culminated in secondary necrosis. Treatment of PRRSV-infected macrophages with Z-Val-DL-Asp-fluoromethylketone indicated that apoptosis late in infection was not essential for efficient virus release. Anti- and pro-apoptotic activities were also observed in PRRSV-infected Marc-145 cells. In conclusion, this study shows that PRRSV stimulates anti-apoptotic pathways in macrophages early in infection and that PRRSV-infected macrophages die by apoptosis late in infection.

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Abbreviations

EMA:

Ethidium monoazide bromide

FITC:

Fluorescein isothiocyanate

GP:

Glycoprotein

hpi:

Hours post-inoculation

mAbs:

Monoclonal antibodies

m.o.i:

Multiplicity of infection

pAbs:

Polyclonal antibodies

PBS:

Phosphate-buffered saline

PRRSV:

Porcine reproductive and respiratory syndrome virus

TCID50 :

Tissue culture infectious dose with a 50% end point

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling

UV:

Ultraviolet

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Acknowledgments

The authors would like to thank Chantal Vanmaercke and Carine Boone for excellent technical assistance. We would like to thank Dr. P. van Rijn and Dr. M.J. Rodriguez for the kind gift of antibodies. S. Costers is supported by a doctoral grant from the special research fund of Ghent University (011D18904). P.L. Delputte is a post-doctoral fellow from the Special Research Fund of Ghent University (B/06524).

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  1. Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium

    Sarah Costers, David J. Lefebvre, Peter L. Delputte & Hans J. Nauwynck

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  1. Sarah Costers
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  2. David J. Lefebvre
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  3. Peter L. Delputte
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  4. Hans J. Nauwynck
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Correspondence to Sarah Costers.

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P. L. Delputte and H. J. Nauwynck share the senior authorship.

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Costers, S., Lefebvre, D.J., Delputte, P.L. et al. Porcine reproductive and respiratory syndrome virus modulates apoptosis during replication in alveolar macrophages. Arch Virol 153, 1453–1465 (2008). https://doi.org/10.1007/s00705-008-0135-5

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  • DOI: https://doi.org/10.1007/s00705-008-0135-5

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