Equine herpesvirus 1: phylogenic analysis in France & new approaches for antiviral therapy
Résumé
Among the 9 herpesviruses described in equids, the equine herpesvirus 1 is particularly pathogenic for equine species. It can cause respiratory disorders, abortion, neonatal foal death and neurological disease. As current vaccines do not provide full protection against severe symptoms, EHV-1 represents a major threat for the horse industry, causing serious economic losses every year. Different tools are available or need to be developed in order to improve outbreak management.
In this report, we will describe the importance of molecular surveillance of strains circulating after performing a phylogenic analysis of strains isolated from 2012 to 2018, including 2018 major EHV-1 crisis [1]. This study allowed the comparison of three different tools including the typing of the well known A2254G ORF30 mutation, the complete ORF30 sequencing and the Multi Locus Sequence Analysis tool developed by Garvey et al. (2019) [2].
We will also describe the development of new antiviral strategies using the xCELLigence RTCA system, based on cells impedance measurement [3]. Until now, 3.000 compounds have been screened against EHV-1 KyD strain using this technology. Based on calculation of two mathematical models, 26 compounds were identified as effective against EHV-1. Antiviral effects of these compounds were confirmed by dose-response assays. Among these compounds, 6 were selected as they showed an efficacy similar to ganciclovir which is the most potent antiviral compound until now. Antiviral effects of these compounds were then confirmed on different cell models and against two field strains of EHV-1 recently isolated in our laboratory. Three of the retained compounds had never been described before against herpesviruses and some combinations studies showed good synergy between different compounds.
References:
1. Sutton, G.; Jourdan, M.; Fortier, C.; Maisonnier, V.; Dervin, S.; Marcillaud-Pitel, C.; Legrand, L.; Paillot, R.; Pronost, S. Phylogenic study of Equine Herpesvirus 1 after a major outbreak in France in 2018; 2019;
2. Garvey, M.; Lyons, R.; Hector, R.; Walsh, C.; Arkins, S.; Cullinane, A. Molecular Characterisation of Equine Herpesvirus 1 Isolates from Cases of Abortion, Respiratory and Neurological Disease in Ireland between 1990 and 2017. Pathogens 2019, 8, 7.
3. Thieulent, C.J.; Hue, E.S.; Fortier, C.I.; Dallemagne, P.; Zientara, S.; Munier-Lehmann, H.; Hans, A.; Fortier, G.D.; Pitel, P.-H.; Vidalain, P.-O.; et al. Screening and evaluation of antiviral compounds against Equid alpha-herpesviruses using an impedance-based cellular assay. Virology 2019, 526, 105–116.