INFECTION WITH THEILERIA-ANNULATA INDUCES EXPRESSION OF MATRIX METALLOPROTEINASE-9 AND TRANSCRIPTION FACTOR AP-1 IN BOVINE LEUKOCYTES

Theileria annulata infects bovine leucocytes and results in their reversible transformation such that they become immortalised and metastatic. The present study describes parasite-induced changes in host cell gene expression which have a direct bearing on this transformation process. T. annulata-infected leucocytes produce a number of novel metalloproteinase activities. One of these, previously called B1, is a 97-kDa protein which is secreted in large amounts and has been purified from protein-free, conditioned medium. An antiserum to this enzyme was used to isolate a cDNA clone. The predicted protein sequence of B1 is 81% identical to human matrix metalloproteinase 9 (MMP9), demonstrating that it is the bovine homologue of this enzyme. RNAase protection assays demonstrated that the MMP9 activity, unique to infected cells, is due to increased MMP9 mRNA levels. We also assayed the levels of transcription factor AP-1 and demonstrated that it was constitutively present in increased amounts in Theileria-infected cells. In addition we assayed the level of mRNA encoding c-Fos, a common component of AP-1 and observed that it was indeed up-regulated in infected cells. Since AP-1 is implicated in the control of the cell cycle, and MMP9 can confer metastatic properties, these results are of considerable significance with respect to the transformed phenotype induced by Theileria infection.