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


METHODS
Vero cell cultures.


METHODS
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 alpha (eIF2alpha) 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 eIF2alpha forms, the hallmark of PKR activation, were not increased in IFNalpha-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 IFNalpha.


CONCLUSIONS
The powerful anti-Paramyxovirus activity of type 1 IFNs is mediated by noncanonic pathways.
Leroy
Michaël P-P
MP
Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
Baise
Etienne A
EA
Pire
Grégory A
GA
Desmecht
Daniel J-M
DJ
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000821:virology*; D002522:Chlorocebus aethiops; D003601:Cytotoxicity Tests, Immunologic / Q000662:veterinary; D034281:Dynamins / Q000378:metabolism*; D005434:Flow Cytometry / Q000662:veterinary; D019084:Fluorescent Antibody Technique, Indirect / Q000662:veterinary; D005562:Formazans / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015151:Immunoblotting / Q000662:veterinary; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D029101:Parainfluenza Virus 3, Bovine / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D013778:Tetrazolium Salts / Q000737:chemistry; D014162:Transfection / Q000662:veterinary; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism*
D005562:Formazans; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D013778:Tetrazolium Salts; C079782:MTT formazan; D016899:Interferon-beta; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins; D034281:Dynamins