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bioRxiv · 10.1101/2025.01.21.634112

Characterizing venom resistance in Monodelphis domestica yields new insights into mammalian blood physiology

Holding, M. L.·Disharoon, D.·Haynes, L. M.·Paruchuri, B. C.·Golden, K.·Shavit, J.·Desch, K.·Ginsburg, D.·Sen Gupta, A.·Cruz, Y. P.·Drabeck, D.
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Abstract

Interactions between predators and prey are often characterized by strong selection pressures that shape extreme physiological adaptations. Venom resistance in large-bodied South American opossums (Clade Didelphini) is a striking example, as these marsupials prey on venomous snakes and exhibit remarkable resistance to their venom. While resistance is well documented in Didelphini, relatively little is known about venom resistance in the smaller, more diverse members of Didelphidae, which inhabit the same regions and encounter the same predators. Here, we investigate venom resistance in the small-bodied opossum, Monodelphis domestica, through multi-level physiological assays, examining responses to purified venom components and whole venom from sympatric and allopatric vipers. Our results show M. domestica resists venom-induced disruptions to blood coagulation, retains platelet function in the presence of platelet-disrupting venoms, and inhibits snake venom metalloproteinases. Unexpectedly, we find that M. domestica von Willebrand Factor (VWF) requires increased shear force to elongate, a previously unknown aspect of opossum blood physiology that may contribute to venom resistance and may have relevance to human coagulopathies. These findings expand the extent of venom resistance beyond large-bodied Didelphini, suggesting it is a widespread trait in South American marsupials and providing new insights into venom-mammal coevolution. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/634112v2_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@1efb74forg.highwire.dtl.DTLVardef@ebcb82org.highwire.dtl.DTLVardef@7ddef2org.highwire.dtl.DTLVardef@1b81569_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Holding, M. L., Disharoon, D., Haynes, L. M., Paruchuri, B. C., Golden, K., Shavit, J., Desch, K., Ginsburg, D., Sen Gupta, A., Cruz, Y. P., Drabeck, D.. 2025-01-22. Characterizing venom resistance in Monodelphis domestica yields new insights into mammalian blood physiology. https://doi.org/10.1101/2025.01.21.634112

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