Contribution of MX dynamin, oligoadenylate synthetase, and protein kinase R to anti-paramyxovirus activity of type 1 interferons in vitro

Michaël P.-P. Leroy Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

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Etienne A. Baise Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

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Grégory A. Pire Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

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Daniel J.-M. Desmecht Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

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DOI:
https://doi.org/10.2460/ajvr.68.9.988
Volume/Issue:
Volume 68: Issue 9
Online Publication Date:
01 Sep 2007
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Abstract

Objective—To determine the contribution of MX dynamin, oligoadenylate synthetase (OAS), and double-stranded RNA-dependent protein kinase R (PKR) to the antiviral effects of type 1 interferons (IFNs) against bovine parainfluenza-3 virus (PI-3V) infection of Vero cells.

Sample Population—Vero cell cultures.

Procedures—PI-3V yield was first compared between control and transfected type 1 IFNs– incompetent Vero cells expressing recombinant OAS or MX proteins. Afterwards, phosphorylation of eukaryotic initiation factor 2 α (eIF2α) was used to scale the degree of PKR activation upon infection of Vero cells by PI-3V.

Results—Overexpression of OAS did not result in significantly decreased viral replication. Phosphorylated eIF2α forms, the hallmark of PKR activation, were not increased in IFNα-primed infected Vero cells. Although human MXA contributed to partial blockade of replication of bovine PI-3V, the antiviral effect was not as strong as that of IFNα.

Conclusions and Clinical Relevance—The powerful anti-Paramyxovirus activity of type 1 IFNs is mediated by noncanonic pathways.

Abstract

Objective—To determine the contribution of MX dynamin, oligoadenylate synthetase (OAS), and double-stranded RNA-dependent protein kinase R (PKR) to the antiviral effects of type 1 interferons (IFNs) against bovine parainfluenza-3 virus (PI-3V) infection of Vero cells.

Sample Population—Vero cell cultures.

Procedures—PI-3V yield was first compared between control and transfected type 1 IFNs– incompetent Vero cells expressing recombinant OAS or MX proteins. Afterwards, phosphorylation of eukaryotic initiation factor 2 α (eIF2α) was used to scale the degree of PKR activation upon infection of Vero cells by PI-3V.

Results—Overexpression of OAS did not result in significantly decreased viral replication. Phosphorylated eIF2α forms, the hallmark of PKR activation, were not increased in IFNα-primed infected Vero cells. Although human MXA contributed to partial blockade of replication of bovine PI-3V, the antiviral effect was not as strong as that of IFNα.

Conclusions and Clinical Relevance—The powerful anti-Paramyxovirus activity of type 1 IFNs is mediated by noncanonic pathways.

Contributor Notes

Supported by the Belgian Federal Public Service Health, Food Chain Safety, and Environment (grant S-6042).

The authors thank Ilkka Julkunen, Pierre Kerkhofs, Otto Haller, Ara Hovanessian, Frank Koenen, Michel Georges, Alain Vanderplasschen, Michaël Frese, Georg Kochs, Peter Staeheli, and Otto Haller for assistance with the study.

Address correspondence to Dr. Desmecht.
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Sep 2007
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