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Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications.
J Proteomics. 2016 09 02; 146:34-47.JP

Abstract

Vipera berus berus (Vbb) is the most widely distributed and Vipera ammodytes ammodytes (Vaa) the most venomous viper in Europe. In particular areas of the Old continent their toxic bites constitute a considerable public health problem. To make the current envenomation therapy more effective we have analysed the proteome of Vbb venom and compared it with that of Vaa. We found the proteome of Vbb to be much less complex and to contain smaller levels of particularly snaclecs and sPLA2s. Snaclecs are probably responsible for thrombocytopenia. The neurotoxic sPLA2s, ammodytoxins, are responsible for the most specific feature of the Vaa venom poisoning - induction of signs of neurotoxicity in patients. These molecules were not found in Vbb venom. Both venoms induce haemorrhage and coagulopathy in man. As Vaa and Vbb venoms possess homologous P-III snake venom metalloproteinases, the main haemorrhagic factors, the severity of the haemorrhage is dictated by concentration and specific activity of these molecules. The much greater anticoagulant effect of Vaa venom than that of Vbb venom lies in its higher extrinsic pathway coagulation factor-proteolysing activity and content of ammodytoxins which block the prothrombinase complex formation.

BIOLOGICAL SIGNIFICANCE

Envenomations by venomous snakes constitute a considerable public health problem worldwide, and also in Europe. In the submitted work we analysed the venom proteome of Vipera berus berus (Vbb), the most widely distributed venomous snake in Europe and compared it with the venom proteome of the most venomous viper in Europe, Vipera ammodytes ammodytes (Vaa). We have offered a possible explanation, at the molecular level, for the differences in clinical pictures inflicted by the Vbb and Vaa venoms. We have provided an explanation for the effectiveness of treatment of Vbb envenomation by Vaa antiserum and explained why full protection of Vaa venom poisoning by Vbb antiserum should not be always expected, especially not in cases of severe poisoning. The latter makes a strong case for Vaa antiserum production as we are faced with its shortage due to ceasing of production of two most frequently used products.

Authors+Show Affiliations

Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia; Jožef Stefan International Postgraduate School, Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia.Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia.Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Croatia.University Medical Centre Ljubljana, Division of Pediatrics, Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. Electronic address: igor.krizaj@ijs.si.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27327134

Citation

Latinović, Zorica, et al. "Venomics of Vipera Berus Berus to Explain Differences in Pathology Elicited By Vipera Ammodytes Ammodytes Envenomation: Therapeutic Implications." Journal of Proteomics, vol. 146, 2016, pp. 34-47.
Latinović Z, Leonardi A, Šribar J, et al. Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications. J Proteomics. 2016;146:34-47.
Latinović, Z., Leonardi, A., Šribar, J., Sajevic, T., Žužek, M. C., Frangež, R., Halassy, B., Trampuš-Bakija, A., Pungerčar, J., & Križaj, I. (2016). Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications. Journal of Proteomics, 146, 34-47. https://doi.org/10.1016/j.jprot.2016.06.020
Latinović Z, et al. Venomics of Vipera Berus Berus to Explain Differences in Pathology Elicited By Vipera Ammodytes Ammodytes Envenomation: Therapeutic Implications. J Proteomics. 2016 09 2;146:34-47. PubMed PMID: 27327134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications. AU - Latinović,Zorica, AU - Leonardi,Adrijana, AU - Šribar,Jernej, AU - Sajevic,Tamara, AU - Žužek,Monika C, AU - Frangež,Robert, AU - Halassy,Beata, AU - Trampuš-Bakija,Alenka, AU - Pungerčar,Jože, AU - Križaj,Igor, Y1 - 2016/06/17/ PY - 2016/04/18/received PY - 2016/06/14/revised PY - 2016/06/15/accepted PY - 2016/6/22/entrez PY - 2016/6/22/pubmed PY - 2017/11/29/medline KW - Neurotoxicity KW - Proteome KW - Snake venom KW - Thrombocytopenia KW - Vipera ammodytes ammodytes KW - Vipera berus berus SP - 34 EP - 47 JF - Journal of proteomics JO - J Proteomics VL - 146 N2 - UNLABELLED: Vipera berus berus (Vbb) is the most widely distributed and Vipera ammodytes ammodytes (Vaa) the most venomous viper in Europe. In particular areas of the Old continent their toxic bites constitute a considerable public health problem. To make the current envenomation therapy more effective we have analysed the proteome of Vbb venom and compared it with that of Vaa. We found the proteome of Vbb to be much less complex and to contain smaller levels of particularly snaclecs and sPLA2s. Snaclecs are probably responsible for thrombocytopenia. The neurotoxic sPLA2s, ammodytoxins, are responsible for the most specific feature of the Vaa venom poisoning - induction of signs of neurotoxicity in patients. These molecules were not found in Vbb venom. Both venoms induce haemorrhage and coagulopathy in man. As Vaa and Vbb venoms possess homologous P-III snake venom metalloproteinases, the main haemorrhagic factors, the severity of the haemorrhage is dictated by concentration and specific activity of these molecules. The much greater anticoagulant effect of Vaa venom than that of Vbb venom lies in its higher extrinsic pathway coagulation factor-proteolysing activity and content of ammodytoxins which block the prothrombinase complex formation. BIOLOGICAL SIGNIFICANCE: Envenomations by venomous snakes constitute a considerable public health problem worldwide, and also in Europe. In the submitted work we analysed the venom proteome of Vipera berus berus (Vbb), the most widely distributed venomous snake in Europe and compared it with the venom proteome of the most venomous viper in Europe, Vipera ammodytes ammodytes (Vaa). We have offered a possible explanation, at the molecular level, for the differences in clinical pictures inflicted by the Vbb and Vaa venoms. We have provided an explanation for the effectiveness of treatment of Vbb envenomation by Vaa antiserum and explained why full protection of Vaa venom poisoning by Vbb antiserum should not be always expected, especially not in cases of severe poisoning. The latter makes a strong case for Vaa antiserum production as we are faced with its shortage due to ceasing of production of two most frequently used products. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/27327134/Venomics_of_Vipera_berus_berus_to_explain_differences_in_pathology_elicited_by_Vipera_ammodytes_ammodytes_envenomation:_Therapeutic_implications_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(16)30259-7 DB - PRIME DP - Unbound Medicine ER -