viruses Review Viral Equine Encephalitis, a Growing Threat to the Horse Population in Europe? Sylvie Lecollinet 1,2,* , Stéphane Pronost 2,3,4, Muriel Coulpier 1,Cécile Beck 1,2 , Gaelle Gonzalez 1, Agnès Leblond 5 and Pierre Tritz 2,6,7 1 UMR (Unité Mixte de Recherche) 1161 Virologie, Anses (the French Agency for Food, Environmental and Occupational Health and Safety), INRAE (French National Institute of Agricultural, Food and Environmental Research), Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, France; [email protected] (M.C.); [email protected] (C.B.); [email protected] (G.G.) 2 RESPE (Réseau d’épidémio-surveillance en pathologie équine), 14280 Saint-Contest, France; [email protected] (S.P.); [email protected] (P.T.) 3 LABÉO, 14280 Saint-Contest, France 4 BIOTARGEN, UNICAEN, NORMANDIE UNIV, 14000 Caen, France 5 UMR EPIA (Epidémiologie des Maladies Animales et Zoonotiques), INRAE, VetAgro Sup, Université de Lyon, 69280 Marcy L’Etoile, France; [email protected] 6 Clinique Vétérinaire, 19 rue de Créhange, 57380 Faulquemont, France 7 AVEF (Association Vétérinaire Equine Française), Committee on Infectious Diseases, 75011 Paris, France * Correspondence: [email protected]; Tel.: +33-143967111 Received: 1 October 2019; Accepted: 17 December 2019; Published: 24 December 2019 Abstract: Neurological disorders represent an important sanitary and economic threat for the equine industry worldwide. Among nervous diseases, viral encephalitis is of growing concern, due to the emergence of arboviruses and to the high contagiosity of herpesvirus-infected horses. The nature, severity and duration of the clinical signs could be different depending on the etiological agent and its virulence. However, definite diagnosis generally requires the implementation of combinations of direct and/or indirect screening assays in specialized laboratories. The equine practitioner, involved in a mission of prevention and surveillance, plays an important role in the clinical diagnosis of viral encephalitis. The general management of the horse is essentially supportive, focused on controlling pain and inflammation within the central nervous system, preventing injuries and providing supportive care. Despite its high medical relevance and economic impact in the equine industry, vaccines are not always available and there is no specific antiviral therapy. In this review, the major virological, clinical and epidemiological features of the main neuropathogenic viruses inducing encephalitis in equids in Europe, including rabies virus (Rhabdoviridae), Equid herpesviruses (Herpesviridae), Borna disease virus (Bornaviridae) and West Nile virus (Flaviviridae), as well as exotic viruses, will be presented. Keywords: encephalitis; arbovirus; rabies; Equid herpesviruses; Borna disease virus; West Nile virus; horses 1. Introduction Neurological disorders represent an important sanitary and economic threat to the equine industry worldwide. Even mild nervous deficits can result in poor performances and long recovery of athletic horses, while severe clinical signs can induce life-threatening injuries in infected horses and may expose owners, veterinarians and care providers to significant risks [1]. Few surveys have been carried out to evaluate the burden of neurological diseases in horses and were performed almost 20 years ago. They indicated that neurological affections accounted as the fifth cause of death (8%) in Viruses 2020, 12, 23; doi:10.3390/v12010023 www.mdpi.com/journal/viruses Viruses 2020, 12, 23 2 of 29 Viruses 2019, 11, x FOR PEER REVIEW 2 of 30 adult horses, behind foaling (24%), digestive (21%), locomotor (21%), and cardiovascular (9%) causes. Inadult two studieshorses, behind performed foaling in (24%), Australia digestive and in (21%), France, locomotor neurological (21%), diseasesand cardiovascular were first (9%) attributed causes. to traumaIn two (26% studies to 34%), performed congenital in Australia malformations and in France, (19% to neurological 20%), while diseases inflammation were andfirst infectionattributed were to reportedtrauma in(26% 6% to to 34%), 17% ofcongenital horses with malformations neurological (19% conditions to 20%), [while2–4]. inflammation Early recognition and infection of neurological were infectiousreported diseasesin 6% to may17% increaseof horses the with chance neurological of a positive conditions outcome [2–4]. and Early is key recognition to the implementation of neurological of coordinatedinfectious diseases management may increase measures the designed chance of to a preventpositive large-scaleoutcome and outbreaks is key to when the implementation highly contagious of pathogens,coordinated such management as equid herpesviruses, measures designed are involved. to prevent Many large-scale neurotropic outbreaks viruses when aff highlyecting contagious equines are alsopathogens, significant such human as equid pathogens herpesviruses, and rapid are involv identificationed. Many of neurotropic zoonotic virusesviruses inaffecting horses equines is pivotal are in also significant human pathogens and rapid identification of zoonotic viruses in horses is pivotal in their surveillance and in the control of corresponding human viral diseases [5]. their surveillance and in the control of corresponding human viral diseases [5]. Multiple neuropathogenic pathogens, either viruses, bacteria or protozoa, can induce an important Multiple neuropathogenic pathogens, either viruses, bacteria or protozoa, can induce an inflammation of the central nervous system (CNS). Bacterial meningitis are common neurological important inflammation of the central nervous system (CNS). Bacterial meningitis are common infections in foals, while neuroborreliosis, listeriosis and Equine Protozoal Myeloencephalitis neurological infections in foals, while neuroborreliosis, listeriosis and Equine Protozoal areMyeloencephalitis rare and difficult are to rare diagnose and difficult in equines to diagnose [1]. Asin equines far as viruses[1]. As far are as concerned, viruses are Rabiesconcerned, virus , EquidRabies alphaherpesvirus virus, Equid alphaherpesvirus 1 (EHV-1), West 1 Nile(EHV-1), virus andWest relatedNile virus flaviviruses and related (Japanese flaviviruses Encephalitis (Japanese virus, Saint-LouisEncephalitis Encephalitis virus, Saint- virusLouisand EncephalitisMurray Valleyvirus Encephalitisand Murray virusValley), MammalianEncephalitis 1virus orthobornavirus), Mammalianand 1 neurotropicorthobornavirus alphaviruses and neurotropic (Eastern, alphaviruses Western and ( VenezuelanEastern, Western Equine and Encephalitis Venezuelan Virus Equinespecies) Encephalitis are the Virus most largelyspecies) described are the most neuropathogenic largely described viruses neuropathogenic (Figure1). viruses (Figure 1). FigureFigure 1. 1. MajorMajor viruses causing causing encephalitis encephalitis in inequines. equines. Virus Virus classification classification according according to ICTV to 2019 ICTV 2019nomenclature nomenclature [6], [6structure], structure and and genome genome organisation organisation are are presented presented for for viruses viruses belonging belonging to to HerpesviridaeHerpesviridae, ,Rhabdoviridae Rhabdoviridae,, FlaviviridaeFlaviviridae, Bornaviridae andand TogaviridaeTogaviridae (adapted(adapted from from ViralZone ViralZone [7]). [7]). WNV:WNV: West West Nile Nile virus; virus; TBEV: TBEV: Tick-Borne Tick-Borne encephalitisencephalitis virus; LIV: Louping ill ill virus; virus; JEV: JEV: Japanese Japanese encephalitisencephalitis virus; virus; EEEV: EEEV: Eastern Eastern equineequine encephalitisencephalitis virus; VEEV: Venezuelan equine equine encephalitis encephalitis virus;virus; WEEV: WEEV: Western Western equine equine encephalitis encephalitis virus,virus, DS:DS : double-stranded,double-stranded, SS SS: : single-stranded. EquineEquine neuropathogenic neuropathogenic viruses ge generallynerally induce induce encephalitis encephalitis or ormyeloencephalitis, myeloencephalitis, which which is an is aninflammation inflammation of ofthe the central central nervous nervous system system (cortex, (cortex, brain brainstem, stem,and cerebellum) and cerebellum) and/or of and the/or spinal of the spinalcord cordcharacterized characterized by large by large or multifocal or multifocal infiltrations infiltrations of ofmononuclear mononuclear cells cells (Figure (Figure 2d).2d). Infected Infected animalsanimals may may experience experience behavioral behavioral change, change, as as well well as as balance, balance, posture posture and and gait gait deficits deficits (Figure (Figure2a–c) 2a–c) [ 1 ]. [1]. Neurological examination, including testing of reflexes, evaluating postures and movements, is Neurological examination, including testing of reflexes, evaluating postures and movements, is key key in the clinical approach and allows assessing the course of disease and therefore its prognosis and in the clinical approach and allows assessing the course of disease and therefore its prognosis and response to therapeutic options. However, it is worth to note that such neurological examination and Viruses 2019, 11, x FOR PEER REVIEW 2 of 30 adult horses, behind foaling (24%), digestive (21%), locomotor (21%), and cardiovascular (9%) causes. In two studies performed in Australia and in France, neurological diseases were first attributed to trauma (26% to 34%), congenital malformations (19% to 20%), while inflammation and infection were reported in 6% to 17%