The tissue-invasive nematode Onchocerca volvulus causes skin and eye pathology in human
onchocerciasis. While the adult females reside sessile in subcutaneous nodules, the microfilariae are abundantly released from the nodules, males and juvenile worms migrate through the host tissue. Matrix-degrading metallo- and
serine proteinases have been detected in excretory-secretory worm products that may be essential for migration of the mobile stages. In this study, a 1713bp long
cDNA encoding for a putative
proteinase of O.
volvulus has been isolated. The predicted
protein sequence includes a
signal peptide indicating secretion to the extracellular space, a propeptide, an
astacin-like
protease domain, an
EGF-like and a CUB-domain, thereby identifying the
protein as a member of the
astacin family of
zinc endopeptidases. Onchoastacin, Ov-AST-1, is most closely related to a subfamily comprising nematode astacins including Caenorhabditis and Ancylostoma. Ov-AST-1 was expressed as a
recombinant protein in baculovirus-infected insect cells and exhibited enzymatic activity. The exposure of onchoastacin to the host immune system is indicated by demonstration of
IgG reacting with the recombinant Ov-AST-1 and with two
peptides of the
protein. Since a homologous
metalloproteinase is part of a promising hookworm
vaccine, Ov-AST-1 may be a candidate for intervention strategies in filarial
infections.