Fiche publication
Date publication
août 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien
Tous les auteurs :
Sorel O, Tuddenham L, Myster F, Palmeira L, Kerkhofs P, Pfeffer S, Vanderplasschen A, Dewals BG
Lien Pubmed
Résumé
Alcelaphine herpesvirus 1 (AlHV-1) is a gamma-herpesvirus (gamma-HV) carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces a fatal lymphoproliferative disease named malignant catarrhal fever (MCF) in many ruminants, including cattle and the rabbit model. Latency has been shown to be essential for MCF induction. However, the mechanisms causing the activation and proliferation of infected CD8+ T cells are unknown. Many gamma-HVs express microRNAs (miRNAs). These small noncoding RNAs can regulate expression of host or viral target genes involved in various pathways and are thought to facilitate viral infection and/or mediate activation and proliferation of infected lymphocytes. AlHV-1 genome has been predicted to encode a large number of miRNAs. However, their precise contribution in viral infection and pathogenesis in vivo remains unknown. Here, using small RNAs cloning and sequencing we identified 36 potential miRNAs expressed in a lymphoblastoid cell line propagated from a calf infected with AlHV-1 and developing MCF. Among the sequenced candidate miRNAs, 32 were expressed on the reverse strand of the genome in two main clusters. The expression of these 32 viral miRNAs was further validated using northern blot and qRT-PCR in lymphoid organs of MCF-developing calves or rabbits. To determine the concerted contribution in MCF of 28 viral miRNAs clustered in the non-protein-coding region of the AlHV-1 genome, a recombinant virus was produced. The absence of these 28 miRNAs did not affect viral growth in vitro or MCF induction in rabbits, indicating that the AlHV-1 miRNAs clustered in this non-protein-coding genomic region are dispensable MCF induction.
Référence
J Gen Virol. 2015 Aug 28
