The asp viper Vipera aspis aspis is a venomous snake found in France, and despite its medical importance, the complete toxin repertoire produced is unknown. Here, we used a venomics approach to decipher the composition of its venom. Transcriptomic analysis revealed 80 venom-annotated sequences grouped into 16 gene families. Among the most represented toxins were snake venom metalloproteases (23%), phospholipases A2 (15%), serine proteases (13%), snake venom metalloprotease inhibitors (13%) and C-type lectins (12%). LC-MS of venoms revealed similar profiles regardless of the method of extraction (milking vs defensive bite). Proteomic analysis validated 57 venom-annotated transcriptomic sequences (>70%), including one for each of the 16 families, but also identified 7 sequences not initially annotated as venom proteins, including a serine protease, a disintegrin, a glutaminyl-peptide cyclotransferase, a proactivator polypeptide-like and 3 aminopeptidases. Interestingly, phospholipases A2 were the dominant proteins in the venom, among which included an ammodytoxin B-like sequence, which may explain the reported neurotoxicity following some asp viper envenomations. In total, 87 sequences were retrieved from the Vipera aspis aspis transcriptome and proteome, constituting a valuable resource that will help in understanding the toxinological basis of clinical signs of envenoming and for the mining of useful pharmacological compounds. BIOLOGICAL SIGNIFICANCE: The asp viper (Vipera aspis aspis) causes several hundred envenomations annually in France, including unusual cases with neurological signs, resulting in one death per year on average. Here, we performed a proteotranscriptomic analysis of V. a. aspis venom in order to provide a better understanding of its venom composition. We found that, as in other Vipera species, phospholipase A2 dominates in the venom, and the presence of a sequence related to ammodytoxin B may explain the reported neurotoxicity following some asp viper envenomations. Thus, this study will help in informing the toxinological basis of clinical signs of envenoming.

中文翻译：

---

毒蛇vi蛇毒的毒害学原理来自法国的毒蛇as蛇毒。

毒蛇毒蛇毒蛇毒蛇是在法国发现的有毒蛇，尽管其具有医学重要性，但尚不清楚产生的完整毒素库。在这里，我们使用了一种经济学方法来解密其毒液的成分。转录组分析揭示了80个带有毒液注释的序列，分为16个基因家族。其中最具代表性的毒素是蛇毒金属蛋白酶（23％），磷脂酶A2（15％），丝氨酸蛋白酶（13％），蛇毒金属蛋白酶抑制剂（13％）和C型凝集素（12％）。不论提取方法（挤奶还是防御性咬伤），毒液的LC-MS均显示相似的特征。蛋白质组学分析验证了57个带毒液注释的转录组序列（> 70％），包括16个家族中的每个，但还鉴定了7个最初未被注释为毒液蛋白的序列，包括丝氨酸蛋白酶，整联蛋白，谷氨酰胺基肽环转移酶，促活化剂多肽样和3个氨基肽酶。有趣的是，磷脂酶A2是毒液中的主要蛋白，其中包括一种类似于氨毒素B的序列，这可能解释了一些毒蛇毒后的神经毒性。总共从87蛇天冬氨酸转录组和蛋白质组中检索到87个序列，构成了宝贵的资源，将有助于了解毒蛇毒的临床体征的毒理学基础，并有助于挖掘有用的药理化合物。生物学意义：在法国，asp毒蛇（Vipera aspis aspis）每年引起数百次毒死，包括具有神经系统症状的异常病例，平均每年导致一人死亡。这里，我们对V. a。进行了蛋白转录组学分析。为了更好地了解其毒液成分，使用aspis毒液。我们发现，如同在其他per蛇物种中一样，磷脂酶A2在毒液中占主导地位，与氨甲毒素B相关的序列的存在可能解释了某些asp毒蛇毒化后的神经毒性。因此，该研究将有助于告知毒性临床症状的毒素学基础。