Neutrophil extracellular traps offer a new therapeutic target for elephant endotheliotropic herpes virus-hemorrhagic disease (EEHV-HD).

Elephant populations are threatened by elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD), a fast-acting infection that often kills very young elephants before they reach maturity. Because it strikes calves at a critical age for survival of the species, EEHV-HD is a major challenge for global conservation. Understanding how the disease causes such severe illness is essential to improving outcomes. In other hemorrhagic diseases, dangerous blood clots form when immune cells release sticky webs of DNA called neutrophil extracellular traps (NETs). We investigate whether this process occurs in elephants with EEHV-HD. Here we show, for the first time, that elephant heterophils (neutrophils) release NETs when stimulated, including by plasma from sick elephants. Tissue samples from fatal cases show large amounts of NETs, suggesting they play a harmful role in disease progression. Encouragingly, known NET inhibitors prevent this response in vitro. Our findings reveal that uncontrolled NET formation likely contributes to EEHV-HD and identify a new potential treatment strategy. Blocking NETs could be combined with existing therapies to improve survival of affected calves, offering a promising way to support elephant health and conservation.