Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective antiviral agent against respiratory syncytial virus.
A dose-dependent decrease in infectivity was observed on introduction of eosinophils into suspensions of respiratory syncytial virus group B (RSV-B). This antiviral effect was reversed by ribonuclease inhibitor, suggesting a role for the eosinophil secretory ribonucleases. Recombinant eosinophil-derived neurotoxin (rhEDN), the major eosinophil ribonuclease, promoted a dose-dependent decrease in RSV-B infectivity, with a 40-fold reduction observed in response to 50 nM rhEDN. Ribonucleolytically inactivated rhEDN (rhEDNdK38) had no antiviral activity. Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated loss of viral genomic RNA in response to rhEDN, suggesting that this protein promotes the direct ribonucleolytic destruction of extracellular virions. Ribonuclease A had no antiviral activity even at approximately 1000-fold higher concentrations, suggesting that rhEDN has unique features other than ribonuclease activity that are crucial to its effectiveness. These results suggest that rhEDN may have potential as a therapeutic agent for prevention or treatment of disease caused by RSV.
Domachowske
J B
JB
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dyer
K D
KD
Bonville
C A
CA
Rosenberg
H F
HF
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010926:Placental Hormones / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects* / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D012260:Ribonucleases; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D010926:Placental Hormones; D011506:Proteins; D011993:Recombinant Fusion Proteins; C022052:placental ribonuclease inhibitor; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D012259:Ribonuclease, Pancreatic