Here we describe and compare the venomic and antivenomic characteristics of both neonate and adult Prairie Rattlesnake (Crotalus viridis viridis)
venoms. Although both neonate and adult
venoms contain unique components, similarities among
protein family content were seen. Both neonate and adult
venoms consisted of
myotoxin,
bradykinin-potentiating
peptide (BPP),
phospholipase A2 (PLA2), Zn(2+)-dependent
metalloproteinase (SVMP),
serine proteinase,
L-amino acid oxidase (LAAO),
cysteine-rich secretory
protein (CRISP) and
disintegrin families. Quantitative differences, however, were observed, with
venoms of adults containing significantly higher concentrations of the non-enzymatic toxic compounds and
venoms of neonates containing higher concentrations of pre-digestive enzymatic
proteins such as SVMPs. To assess the relevance of this
venom variation in the context of
snakebite and
snakebite treatment, we tested the efficacy of the common
antivenom CroFab® for recognition of both adult and neonate
venoms in vitro. This comparison revealed that many of the major
protein families (SVMPs, CRISP, PLA2,
serine proteases, and LAAO) in both neonate and adult
venoms were immunodepleted by the
antivenom, whereas
myotoxins, one of the major toxic components of C. v. viridis
venom, in addition to many of the small
peptides, were not efficiently depleted by CroFab®. These results therefore provide a comprehensive catalog of the
venom compounds present in C. v. viridis
venom and new molecular insight into the potential efficacy of CroFab® against human envenomations by one of the most widely distributed rattlesnake species in North America.
BIOLOGICAL SIGNIFICANCE: Comparative proteomic analysis of
venoms of neonate and adult Prairie Rattlesnake (Crotalus viridis viridis) from a discrete population in Colorado revealed a novel pattern of ontogenetic shifts in toxin composition for viperid snakes. The observed stage-dependent decrease of the relative content of
disintegrins, catalytically active D49-PLA2s,
L-amino acid oxidase, and SVMPs, and the concomitant increase of the relative abundance of paralytic small basic
myotoxins and ohanin-like toxin, and hemostasis-disrupting
serine proteinases, may represent an age-dependent strategy for securing prey and avoiding injury as the snake switches from small ectothermic prey and newborn rodents to larger endothermic prey. Such age-dependent shifts in
venom composition may be relevant for
antivenom efficacy and treatment of
snakebite. However, applying a second-generation antivenomics approach, we show that CroFab®, developed against
venom of three Crotalus and one Agkistrodon species, efficiently immunodepleted many, but not all, of the major compounds present in neonate and adult C. v. viridis
venoms.