Auto-resistance toward snake venom metalloproteases in North American pitvipers

Hill, Kaleb

Mackessy, Stephen P.

School of Biological Sciences

University of Northern Colorado

Greeley, Colorado USA

Analysis of natural snake venom inhibitors in snake blood began in the 18th century with the pioneering work of Fontana on European vipers. Serum resistance to conspecific and heterospecific venoms has subsequently been identified in many snakes, but results vary. Many of these snakes demonstrating resistance are either allopatric or distantly related, making the ecological explanation of this resistance unclear. Auto-resistance to one’s own venom for protection against self-envenomation has been suggested to be provided by endogenous antibodies to the venom components or by other serum-based protective molecules. Toxin resistance could develop in venomous organisms resulting from the physiological production of their own venom, but this connection remains unclear, and it is uncertain if mechanisms may be broadly protective against other species' venoms. North America has many species of pitvipers; these snakes are commonly social animals, often communally hibernating and providing maternal care to young, and they are not known cannibalize other snakes. Therefore, predator avoidance does not seem to be a driving factor favoring resistance. In general, North American pitviper venoms contain high levels of snake venom metalloproteases. Using microassays containing venom and serum from 44 individuals representing 3 genera and 17 species of pitvipers, I measured serum ability to inhibit SVMP activity. Serum reduced SVMP activity by 40% or higher when assayed with the snake’s own venom. Resistance levels can vary between snakes, and individuals from the same population demonstrated varying levels of resistance to conspecific venoms. Several species displayed broad resistance against multiple species’ venoms, while other species had high resistance to only a few venoms. Auto-resistance in pitvipers thus may provide protection against biochemically similar toxins that other snake species produce, and this system can serve as a model for testing auto-resistance in other venomous organisms.