Toxicity evolution of Vipera aspis aspis venom: identification and molecular modeling of a novel phospholipase A2 heterodimer neurotoxin1

Jan, Virginie; Maroun, Rachid C.; Robbe-Vincent, A.; Haro, Luc de; Choumet, Valérie

doi:10.1016/s0014-5793(02)03205-2

Cited by 48 publications

(23 citation statements)

References 29 publications

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“…The venom gland mRNA of this neurotoxic Vaa snake was sequenced and led to the identification of two neurotoxins, AtxB, an isoform of ammodytoxin previously described only in the venom of Vamam , and vaspin, a neurotoxin similar to PLA2-I and vipoxin [21], composed of two subunits, an acidic one called vaspin A (vasA) and a basic one, called vaspin B (vasB). Among the genes encoding the venom PLA 2 s of the same neurotoxic snake were genes encoding ammodytin I1 (AmI1), ammodytin I2 (AmI2), vaspin and the three isoforms of Atx, as well as a retrotransposon reported to be a phylogenetic marker of the genome of Vipera ammodytes species [22], [23]; a true Vaa genome only contains genes encoding AmI1, AmI2 and vaspin from this list.…”

Section: Introductionmentioning

confidence: 99%

Reappraisal of Vipera aspis Venom Neurotoxicity

et al. 2007

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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.

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Section: Introductionmentioning

confidence: 99%

Reappraisal of Vipera aspis Venom Neurotoxicity

et al. 2007

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“…We showed, by RT‐PCR, that the venom of this snake contained two neurotoxins. One was monomeric and identical with ammodytoxin B, and the other (vaspin) was heterodimeric and similar to vipoxin, the toxic complex of Vipera ammodytes meridionalis snake venom [13]. These two toxins were responsible for the symptoms of neurotoxicity observed after envenomation [13].…”

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confidence: 99%

Sequences and structural organization of phospholipase A₂ genes from Vipera aspis aspis, V. aspis zinnikeri and Vipera berus berus venom

Guillemin

Bouchier

Garrigues

et al. 2003

European Journal of Biochemistry

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We used a PCR-based method to determine the genomic DNA sequences encoding phospholipases A 2 (PLA2s) from the venoms of Vipera aspis aspis (V. a. aspis), Vipera aspis zinnikeri (V. a. zinnikeri), Vipera berus berus (V. b. berus) and a neurotoxic V. a. aspis snake (neurotoxic V. a. aspis) from a population responsible for unusual neurotoxic envenomations in south-east France. We sequenced five groups of genes, each corresponding to a different PLA2. The genes encoding the A and B chains of vaspin from the neurotoxic V. a. aspis, PLA2-I from V. a. zinnikeri, and the anticoagulant PLA2 from V. b. berus are described here. Single nucleotide differences leading to amino-acid substitutions were observed both between genes encoding the same PLA2 and between genes encoding different PLA2s. These differences were clustered in exons 3 and 5, potentially altering the biological activities of PLA2. The distribution and characteristics of the PLA2 genes differed according to the species or subspecies. We characterized for the first time genes encoding neurotoxins from the V. a. aspis and V. b. berus snakes of central France. Genes encoding ammodytins I1 and I2, described previously in Vipera ammodytes ammodytes (V. am. ammodytes), were also present in V. a. aspis and V. b. berus. Three different ammodytin I1 gene sequences were characterized: one from V. b. berus, the second from V. a. aspis, V. a. zinnikeri and the neurotoxic V. a. aspis, and the third from the neurotoxic V. a. aspis. This third sequence was identical with the reported sequence of the V. am. ammodytes ammodytin I1 gene. Genes encoding monomeric neurotoxins of V. am. ammodytes venom, ammodytoxins A, B and C, and the Bov-B LINE retroposon, a phylogenetic marker found in V. am. ammodytes genome, were identified in the genome of the neurotoxic V. a. aspis. These results suggest that the population of neurotoxic V. a. aspis snakes from south-east France may have resulted from interbreeding between V. a. aspis and V. am. ammodytes.

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“…The phospholipase A2 neurotoxins present in the venom of some asp vipers in France are similar to the neurotoxins (vipoxin and ammodytoxins) found in Vipera ammodytes (Table 1) [3,4,5,6,7,8,9,10,11,12]. Venom from Vipera ammodytes is used to immunize horses for production of Viperfav*.…”

Section: Treatment Protocol Used For Viper Envenomation In Mainlanmentioning

confidence: 84%

“…Both contain kininogenase (hypotensive bradykinin-releasing enzyme), prothrombin-activating factors, proteases, and hyaluronidases. Neurotoxins of the phospholipase A2 type have been found in the venom of some populations of Vipera aspis, but never in the venom of Vipera berus (Table 1) [3,4,5,6,7,8,9,10,11,12]. …”

Section: Composition Of Venom and Circumstances Related To Envenommentioning

confidence: 99%

Asp Viper (Vipera aspis) Envenomation: Experience of the Marseille Poison Centre from 1996 to 2008

Haro

Glaizal

Tichadou

et al. 2009

Toxins

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A retrospective case review study of viper envenomations collected by the Marseille’s Poison Centre between 1996 and 2008 was performed. Results: 174 cases were studied (52 grade 1 = G1, 90 G2 and 32 G3). G1 patients received symptomatic treatments (average hospital stay 0.96 day). One hundred and six (106) of the G2/G3 patients were treated with the antivenom Viperfav* (2.1+/-0.9 days in hospital), while 15 of them received symptomatic treatments only (plus one immediate death) (8.1+/-4 days in hospital, 2 of them died). The hospital stay was significantly reduced in the antivenom treated group (p < 0.001), and none of the 106 antivenom treated patients had immediate (anaphylaxis) or delayed (serum sickness) allergic reactions. Conclusion: Viperfav* antivenom was safe and effective for treating asp viper venom-induced toxicity.

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Toxicity evolution of Vipera aspis aspis venom: identification and molecular modeling of a novel phospholipase A₂ heterodimer neurotoxin¹

Cited by 48 publications

References 29 publications

Reappraisal of Vipera aspis Venom Neurotoxicity

Reappraisal of Vipera aspis Venom Neurotoxicity

Sequences and structural organization of phospholipase A₂ genes from Vipera aspis aspis, V. aspis zinnikeri and Vipera berus berus venom

Asp Viper (Vipera aspis) Envenomation: Experience of the Marseille Poison Centre from 1996 to 2008

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Toxicity evolution of Vipera aspis aspis venom: identification and molecular modeling of a novel phospholipase A2 heterodimer neurotoxin1

Cited by 48 publications

References 29 publications

Reappraisal of Vipera aspis Venom Neurotoxicity

Reappraisal of Vipera aspis Venom Neurotoxicity

Sequences and structural organization of phospholipase A2 genes from Vipera aspis aspis, V. aspis zinnikeri and Vipera berus berus venom

Asp Viper (Vipera aspis) Envenomation: Experience of the Marseille Poison Centre from 1996 to 2008

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Toxicity evolution of Vipera aspis aspis venom: identification and molecular modeling of a novel phospholipase A₂ heterodimer neurotoxin¹

Sequences and structural organization of phospholipase A₂ genes from Vipera aspis aspis, V. aspis zinnikeri and Vipera berus berus venom