Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications.
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.



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.
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia; Jožef Stefan International Postgraduate School, Ljubljana, Slovenia.
Zorica
Z
Latinović
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Adrijana
A
Leonardi
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Jernej
J
Šribar
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Tamara
T
Sajevic
Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia.
Monika C
MC
Žužek
Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia.
Robert
R
Frangež
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Croatia.
Beata
B
Halassy
University Medical Centre Ljubljana, Division of Pediatrics, Ljubljana, Slovenia.
Alenka
A
Trampuš-Bakija
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Jože
J
Pungerčar
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.
Igor
I
Križaj
D000818:Animals; D000997:Antivenins / Q000737:chemistry / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D045726:Metalloproteases; D054497:Phospholipases A2, Secretory; D020543:Proteome; D013045:Species Specificity; D014757:Viper Venoms / Q000633:toxicity*; D017819:Viperidae
D000997:Antivenins; D020543:Proteome; D014757:Viper Venoms; C068117:ammodytoxin A; D054497:Phospholipases A2, Secretory; D045726:Metalloproteases
Neurotoxicity; Proteome; Snake venom; Thrombocytopenia; Vipera ammodytes ammodytes; Vipera berus berus