In silico prediction of protein-protein interactions between Theileria parva and the Bos taurus Everlyn Muthoni

Abstract

Theileria parva induces pathogenesis, characteristic of cancer cell transformation and associated with invasion, proliferation and altered gene expression of infected bovine host leukocytes. Protein interactions are important for biological functions that underlie processes essential to pathogenesis during infection and can be used to select potential therapeutic targets. Using information on conserved protein interactions in other organisms (interologs), protein interactions and orthologous relationships were predicted between Theileria parva and Bos taurus (the bovine mammalian host). Among the predicted interactions were Theileria’s HSP90 and glutaredoxin-like protein, and bovine c-JUN, AKT1, Rac1, STAT3 and HIF1- proteins, observed as hubs connecting the predicted interactions to protein interactions within host. Bovine proteins were enriched in pathways that reflect known phenotype of Theileria infection such as induction or inhibition of apoptosis signaling, metastasis and tissue invasion, IL-10 signaling, NF-B/IKK activation, PI-3K pathway, TGF- signaling, modulation of immune and inflammatory responses. Support vector machine classifiers trained with the predicted interactions identified known protein interactions with 86.22% accuracy, 84.72% precision, 89.88% sensitivity and 84.39% specificity measures. Predicted interactions provide insight into Theileria- and bovine-encoded interactions that contribute to infection, providing a candidate set for subsequent experimental studies with possible use for defining functional annotation to uncharacterized parasite proteins.