Reappraisal of Vipera aspis Venom Neurotoxicity

Abstract

BackgroundThe variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA2 neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA2 composition of the snakes captured in the same areas.Methodology/Principal FindingsWe conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA2s. We used SELDI technology to study the diversity of PLA2 in various venom samples. Neurological signs (mainly cranial nerve disturbances) were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA2s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA2 venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains.Conclusions/SignificanceThe association of epidemiological studies to genetic, biochemical and immunochemical analyses of snake venoms allowed a good evaluation of the potential neurotoxicity of snake bites. A correlation was found between the expression of neurological symptoms in humans and the intensity of the cross-reaction of venoms with anti-ammodytoxin antibodies, which is correlated with the level of neurotoxin (vaspin and/or ammodytoxin) expression in the venom. The origin of the two recently identified neurotoxic snake populations is discussed according to venom PLA2 genome and transcriptome data.

Snakebite Envenoming: A Public Health Perspective

“…Intravascular hemolysis might also occur, in some cases associated with microthrombi formation (Warrell, 1996). Exceptions to this general trend are envenomings by the South American and some populations of North American rattlesnakes, as well as some viperids in the Old World, which induce neurotoxicity (AzevedoMarques et al, 2009;Ferquel et al, 2007). Despite the existence of these general trends, clinical studies highlight the complexity of snakebite envenoming, as demonstrated by the description of 'unusual' manifestations in cases by some elapids in Asia and South America Manock et al, 2008;Trinh et al, 2010).…”

Systemic pathological effects induced by cobra (Naja naja) venom from geographically distinct origins of Indian peninsula

“…The variation in venom composition and pharmacology has been addressed for different snake venoms at several levels (Chipppaux et al, 1991). Studies on understanding the intra-specific variability of venoms are gaining much attention with the intention of production of efficacious therapeutic antivenom and have been studied extensively (Goncalves, 1956;Glenn et al, 1983;Silveira et al, 1990;Yang et al, 1991;Lomonte and Carmona, 1992;Oguiura et al, 2000;Ferquel et al, 2007).…”

Efficacité variable de l’antivenin Viperfav® pour traiter les envenimations vipérines avec neurotoxicité

“…Les régions de France les plus concernées sont les massif montagneux [2,6,10] et la Vendée [11]. Dans les années 1990, la prise en charge des patients envenimés par des vipères a été améliorée : élaboration d'un tableau de gradation corrélé aux quantités circulantes de venin [1,12,13] ; mise au point d'un antivenin purifié utilisable par voie intraveineuse et ayant prouvé lors d'essais cliniques une excellente tolérance [14] et une efficacité spectaculaire [15] ; découverte de plusieurs populations de vipères aspics neurotoxiques dans le Sud de la France [4,5] et en Italie [6,16]. L'antivenin Viperfav W est produit grâce à l'immunisation de chevaux contre le venin de trois espèces de vipères européennes dont Vipera ammodytes d'Europe de l'est et des Balkans.…”

“…Cependant, des travaux récents ont mis en évidence la présence dans le venin d'une vipère capturée à Font-Romeu de neurotoxines capables d'interagir avec des anticorps antiammoditoxines. Cela amenait les auteurs à prévoir l'observation d'envenimations avec neurotoxicité dans les Pyrénées [6], ce qui est désormais confirmé par notre observation. Tous les travaux publiés font état d'une efficacité du Viperfav W sur les symptômes neurologiques [2,8].…”