The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits.

Détails

ID Serval
serval:BIB_3F98E9A21020
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits.
Périodique
Journal of General Virology
Auteur(s)
Boudry C., Markine-Goriaynoff N., Delforge C., Springael J.Y., de Leval L., Drion P., Russell G., Haig D.M., Vanderplasschen A.F., Dewals B.
ISSN
0022-1317[print], 0022-1317[linking]
Statut éditorial
Publié
Date de publication
2007
Volume
88
Numéro
Pt 12
Pages
3224-3233
Langue
anglais
Résumé
Many gammaherpesviruses encode G-protein-coupled receptors (GPCRs). Several in vivo studies have revealed that gammaherpesvirus GPCRs are important for viral replication and for virus-induced pathogenesis. The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) is carried asymptomatically by wildebeest, but causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species. The A5 ORF of the AlHV-1 genome encodes a putative GPCR. In the present study, we investigated whether A5 encodes a functional GPCR and addressed its role in viral replication and in the pathogenesis of MCF. In silico analysis supported the hypothesis that A5 could encode a functional GPCR as its expression product contained several hallmark features of GPCRs. Expression of A5 as tagged proteins in various cell lines revealed that A5 localizes in cell membranes, including the plasma membrane. Using [35S]GTPgammaS and reporter gene assays, we found that A5 is able to constitutively couple to alpha i-type G-proteins in transfected cells, and that this interaction is able to inhibit forskolin-triggered cAMP response element-binding protein (CREB) activation. Finally, using an AlHV-1 BAC clone, we produced a strain deleted for A5 and a revertant strain. Interestingly, the strain deleted for A5 replicated comparably to the wild-type parental strain and induced MCF in rabbits that was indistinguishable from that of the parental strain. The present study is the first to investigate the role of an individual gene of AlHV-1 in MCF pathogenesis.
Mots-clé
Amino Acid Sequence, Animals, Cattle, Cell Line, Cell Membrane/metabolism, GTP-Binding Protein alpha Subunits/metabolism, Gammaherpesvirinae/pathogenicity, Gammaherpesvirinae/physiology, Genes, Viral/physiology, Malignant Catarrh/metabolism, Malignant Catarrh/virology, Molecular Sequence Data, Open Reading Frames/genetics, Rabbits, Receptors, G-Protein-Coupled/metabolism, Virulence, Virus Replication
Pubmed
Open Access
Oui
Création de la notice
27/10/2010 9:50
Dernière modification de la notice
08/05/2019 17:33
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