Eosinophils, ribonucleases and host defense: Solving the puzzle

The eosinophil ribonucleases eosinophil-derived neurotoxin (EDN/RNase 2) an d eosinophil cationic protein (ECP/RNase 3) are among the major secretory e ffector proteins of human eosinophilic leukocytes, cells whose role in host defense remains controversial and poorly understood. We have recently desc ribed the unusual manner in which this ribonuclease lineage has evolved, wi th extraordinary diversification observed in primate as well as in rodent E DNs and ECPs. The results of our evolutionary studies suggest that the EDN/ ECP ribonucleases are in the process of being tailored for a specific, ribo nuclease-related goal. With this in mind, we have begun to look carefully a t some of the intriguing associations that link eosinophils and their ribon ucleases to disease caused by the single-stranded RNA viral pathogen, respi ratory syncytial virus (RSV). Recent work in our laboratory has demonstrate d that eosinophils can mediate a direct, ribonuclease-dependent reduction i n infectivity of RSV in vitro, and that EDN can function alone as an indepe ndent antiviral agent. The results of this work have led us to consider the possibility that the EDN/ECP ribonucleases represent a heretofore unrecogn ized element of innate and specific antiviral host defense.